[go: up one dir, main page]
Skip to main content
Springer Nature Link
Log in

Molecular Phenotypes of Endothelial Cells in Malignant Tumors

  • Chapter
  • First Online:
Biomarkers of the Tumor Microenvironment

Abstract

Angiogenesis is an essential process for tumor growth, progression, and metastasis, and it is one of the hallmarks of cancer. In addition to being structurally atypical, tumor blood vessels exhibit distinctly abnormal molecular phenotypes compared to their normal counterparts. As noticed by Aird: “The phenotypes of endothelial cells vary in structure and function, in space and time, and health and disease.” The palette of tumor endothelial phenotypes results from the specific conditions that guide the formation of these vessels, including activation of specific signaling pathways and a range of environmental pressures.

The focus of this chapter is to outline the roles endothelial cells play in basic physiological and pathological processes, to provide an overview of the mechanisms of dysregulated tumor angiogenesis, and to point out well-established and some novel molecular markers and phenotypes of tumor endothelial cells. We list key experimental and clinical studies that discuss the clinical relevance of specific molecular markers in predicting prognosis and therapy response, supporting the importance of tumor-associated angiogenesis in pathological processes such as metastasis. In addition to this, we discuss novel therapeutic approaches based on exploiting the molecular specificity of tumor endothelial cells to provide selective and efficient therapies.

Pathological stimulation of endothelial cells in tumors induces abnormal vascular phenotypes with altered function. Molecular markers of tumor endothelial cells can aid in predicting prognosis and response to therapy in cancer

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+
from €37.37 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

Chapter
EUR 29.95
Price includes VAT (France)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
EUR 74.89
Price includes VAT (France)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
EUR 94.94
Price includes VAT (France)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
EUR 137.14
Price includes VAT (France)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

References

  1. Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. 2007;100(2):158–73. https://doi.org/10.1161/01.RES.0000255691.76142.4a.

    Article  CAS  PubMed  Google Scholar 

  2. Krüger-Genge A, et al. Vascular endothelial cell biology: an update. Int J Mol Sci. 2019;20(18):4411. https://doi.org/10.3390/ijms20184411.

    Article  CAS  PubMed Central  Google Scholar 

  3. Aird WC. Molecular heterogeneity of tumor endothelium. Cell Tissue Res. 2009;335:271–81. https://doi.org/10.1007/s00441-008-0672-y.

    Article  CAS  PubMed  Google Scholar 

  4. Aird WC. Endothelial cell heterogeneity. Crit Care Med. 2003;31(4 Suppl):S221–30. https://doi.org/10.1097/01.CCM.0000057847.32590.C1.

    Article  PubMed  Google Scholar 

  5. Jambusaria A, et al. Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation. eLife. 2020;9:e51413. https://doi.org/10.7554/eLife.51413.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Potente M, Mäkinen T. Vascular heterogeneity and specialization in development and disease. Nat Rev Mol Cell Biol. 2017;18(8):477–94. https://doi.org/10.1038/nrm.2017.36.

    Article  CAS  PubMed  Google Scholar 

  7. Gerritsen ME, Printz MP. Sites of prostaglandin synthesis in the bovine heart and isolated bovine coronary microvessels. Circ Res. 1981;49(5):1152–63. https://doi.org/10.1161/01.res.49.5.1152.

    Article  CAS  PubMed  Google Scholar 

  8. Johnson AR. Human pulmonary endothelial cells in culture. Activities of cells from arteries and cells from veins. J Clin Invest. 1980;65(4):841–50. https://doi.org/10.1172/JCI109736.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Kalucka J, et al. Single-cell transcriptome atlas of murine endothelial cells. Cell. 2020;180(4):764–779.e20. https://doi.org/10.1016/j.cell.2020.01.015.

    Article  CAS  PubMed  Google Scholar 

  10. Chi JT, et al. Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci U S A. 2003;100(19):10623–8. https://doi.org/10.1073/pnas.1434429100.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Paik DT, et al. Single-cell RNA sequencing unveils unique transcriptomic signatures of organ-specific endothelial cells. Circulation. 2020;142(19):1848–62. https://doi.org/10.1161/CIRCULATIONAHA.119.041433.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Augustin HG, Koh GY. Organotypic vasculature: from descriptive heterogeneity to functional pathophysiology. Science (New York, NY). 2017;357(6353):eaal2379. https://doi.org/10.1126/science.aal2379.

    Article  CAS  Google Scholar 

  13. Bussmann J, Wolfe SA, Siekmann AF. Arterial-venous network formation during brain vascularization involves hemodynamic regulation of chemokine signaling. Development. 2011;138(9):1717–26. https://doi.org/10.1242/dev.059881.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Matsuoka H, et al. The retinoic acid receptor-related orphan receptor α positively regulates tight junction protein claudin domain-containing 1 mRNA expression in human brain endothelial cells. J Biochem. 2017;161(5):441–50. https://doi.org/10.1093/jb/mvw092.

    Article  CAS  PubMed  Google Scholar 

  15. Gillich A, et al. Capillary cell-type specialization in the alveolus. Nature. 2020;586(7831):785–9. https://doi.org/10.1038/s41586-020-2822-7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115(10):1285–95. https://doi.org/10.1161/CIRCULATIONAHA.106.652859.

    Article  PubMed  Google Scholar 

  17. Pober JS, Sessa WC. Inflammation and the blood microvascular system. Cold Spring Harb Perspect Biol. 2014;7(1):a016345. https://doi.org/10.1101/cshperspect.a016345.

    Article  PubMed  Google Scholar 

  18. Michiels C. Endothelial cell functions. J Cell Physiol. 2003;196(3):430–43. https://doi.org/10.1002/jcp.10333.

    Article  CAS  PubMed  Google Scholar 

  19. Gori T. Endothelial function: a short guide for the interventional cardiologist. Int J Mol Sci. 2018;19(12):3838. https://doi.org/10.3390/ijms19123838.

    Article  CAS  PubMed Central  Google Scholar 

  20. Miura H, Gutterman DD. Human coronary arteriolar dilation to arachidonic acid depends on cytochrome P-450 monooxygenase and Ca2+-activated K+ channels. Circ Res. 1998;83(5):501–7. https://doi.org/10.1161/01.res.83.5.501.

    Article  CAS  PubMed  Google Scholar 

  21. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327(6122):524–6. https://doi.org/10.1038/327524a0.

    Article  CAS  PubMed  Google Scholar 

  22. Loh YC, et al. Overview of the microenvironment of vasculature in vascular tone regulation. Int J Mol Sci. 2018;19(1):120. https://doi.org/10.3390/ijms19010120.

    Article  CAS  PubMed Central  Google Scholar 

  23. Moncada S, Higgs EA, Vane JR. Human arterial and venous tissues generate prostacyclin (prostaglandin x), a potent inhibitor of platelet aggregation. Lancet. 1977;1(8001):18–20. https://doi.org/10.1016/s0140-6736(77)91655-5.

    Article  CAS  PubMed  Google Scholar 

  24. Chien S. Effects of disturbed flow on endothelial cells. Ann Biomed Eng. 2008;36(4):554–62. https://doi.org/10.1007/s10439-007-9426-3.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Garland CJ, Dora KA. EDH: endothelium-dependent hyperpolarization and microvascular signalling. Acta Physiol (Oxf). 2017;219(1):152–61. https://doi.org/10.1111/apha.12649.

    Article  CAS  Google Scholar 

  26. Yanagisawa M, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332(6163):411–5. https://doi.org/10.1038/332411a0.

    Article  CAS  PubMed  Google Scholar 

  27. Cines DB, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91(10):3527–61.

    CAS  PubMed  Google Scholar 

  28. de Graaf JC, et al. Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation. 1992;85(6):2284–90. https://doi.org/10.1161/01.cir.85.6.2284.

    Article  PubMed  Google Scholar 

  29. Sadler JE. Thrombomodulin structure and function. Thromb Haemost. 1997;78(1):392–5.

    Article  CAS  PubMed  Google Scholar 

  30. Denis CV, et al. Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice. Proc Natl Acad Sci U S A. 2001;98(7):4072–7. https://doi.org/10.1073/pnas.061307098.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Eppihimer MJ, et al. Heterogeneity of expression of E- and P-selectins in vivo. Circ Res. 1996;79(3):560–9. https://doi.org/10.1161/01.res.79.3.560.

    Article  CAS  PubMed  Google Scholar 

  32. Salsman VS, et al. Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting T lymphocytes to the tumor microenvironment. PLoS One. 2011;6(5):e20267. https://doi.org/10.1371/journal.pone.0020267.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Young MR. Endothelial cells in the eyes of an immunologist. Cancer Immunol Immunother. 2012;61(10):1609–16. https://doi.org/10.1007/s00262-012-1335-0.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Johnson LA, Jackson DG. Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration. Int Immunol. 2010;22(10):839–49. https://doi.org/10.1093/intimm/dxq435.

    Article  CAS  PubMed  Google Scholar 

  35. Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007;7(10):803–15. https://doi.org/10.1038/nri2171.

    Article  CAS  PubMed  Google Scholar 

  36. Teijaro JR, et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell. 2011;146(6):980–91. https://doi.org/10.1016/j.cell.2011.08.015.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Zhang J, et al. Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization. Cell Metab. 2020;31(6):1136–1153.e7. https://doi.org/10.1016/j.cmet.2020.05.004.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Maishi N, Hida K. Tumor endothelial cells accelerate tumor metastasis. Cancer Sci. 2017;108(10):1921–6. https://doi.org/10.1111/cas.13336.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Geindreau M, Ghiringhelli F, Bruchard M. Vascular endothelial growth factor, a key modulator of the anti-tumor immune response. Int J Mol Sci. 2021;22(9):4871. https://doi.org/10.3390/ijms22094871.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Brat DJ, Van Meir EG. Glomeruloid microvascular proliferation orchestrated by VPF/VEGF: a new world of angiogenesis research. Am J Pathol. 2001;158(3):789–96. https://doi.org/10.1016/S0002-9440(10)64025-4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Nagy JA, et al. Heterogeneity of the tumor vasculature. Semin Thromb Hemost. 2010;36(3):321–31. https://doi.org/10.1055/s-0030-1253454.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Pettersson A, et al. Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Lab Invest. 2000;80(1):99–115. https://doi.org/10.1038/labinvest.3780013.

    Article  CAS  PubMed  Google Scholar 

  43. Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev. 2005;15(1):102–11. https://doi.org/10.1016/j.gde.2004.12.005.

    Article  CAS  PubMed  Google Scholar 

  44. Bennewith KL, Durand RE. Quantifying transient hypoxia in human tumor xenografts by flow cytometry. Cancer Res. 2004;64(17):6183–9. https://doi.org/10.1158/0008-5472.CAN-04-0289.

    Article  CAS  PubMed  Google Scholar 

  45. Kimura H, et al. Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res. 1996;56(23):5522–8.

    CAS  PubMed  Google Scholar 

  46. McDonald DM, Baluk P. Imaging of angiogenesis in inflamed airways and tumors: newly formed blood vessels are not alike and may be wildly abnormal: Parker B. Francis lecture. Chest. 2005;128(6 Suppl):602S–8S. https://doi.org/10.1378/chest.128.6_suppl.602S-a.

    Article  PubMed  Google Scholar 

  47. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473(7347):298–307. https://doi.org/10.1038/nature10144.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Chang YS, et al. Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A. 2000;97(26):14608–13. https://doi.org/10.1073/pnas.97.26.14608.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Cao Z, et al. Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance. Cancer Cell. 2014;25(3):350–65. https://doi.org/10.1016/j.ccr.2014.02.005.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Cao Z, et al. Molecular checkpoint decisions made by subverted vascular niche transform indolent tumor cells into chemoresistant cancer stem cells. Cancer Cell. 2017;31(1):110–26. https://doi.org/10.1016/j.ccell.2016.11.010.

    Article  CAS  PubMed  Google Scholar 

  51. Ghiabi P, et al. Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties. PLoS One. 2014;9(11):e112424. https://doi.org/10.1371/journal.pone.0112424.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Lu J, et al. Endothelial cells promote the colorectal cancer stem cell phenotype through a soluble form of Jagged-1. Cancer Cell. 2013;23(2):171–85. https://doi.org/10.1016/j.ccr.2012.12.021.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Pedrosa AR, et al. Endothelial Jagged1 promotes solid tumor growth through both pro-angiogenic and angiocrine functions. Oncotarget. 2015;6(27):24404–23. https://doi.org/10.18632/oncotarget.4380.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Wieland E, et al. Endothelial Notch1 Activity facilitates metastasis. Cancer Cell. 2017;31(3):355–67. https://doi.org/10.1016/j.ccell.2017.01.007.

    Article  CAS  PubMed  Google Scholar 

  55. Zhu TS, et al. Endothelial cells create a stem cell niche in glioblastoma by providing NOTCH ligands that nurture self-renewal of cancer stem-like cells. Cancer Res. 2011;71(18):6061–72. https://doi.org/10.1158/0008-5472.CAN-10-4269.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Yadav A, et al. Tumor-associated endothelial cells promote tumor metastasis by chaperoning circulating tumor cells and protecting them from anoikis. PLoS One. 2015;10(10):e0141602. https://doi.org/10.1371/journal.pone.0141602.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Beerepoot LV, et al. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol. 2004;15(1):139–45. https://doi.org/10.1093/annonc/mdh017.

    Article  CAS  PubMed  Google Scholar 

  58. Mancuso P, et al. Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood. 2001;97(11):3658–61. https://doi.org/10.1182/blood.v97.11.3658.

    Article  CAS  PubMed  Google Scholar 

  59. Maishi N, et al. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan. Sci Rep. 2016;6:28039. https://doi.org/10.1038/srep28039.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Ohga N, et al. Heterogeneity of tumor endothelial cells: comparison between tumor endothelial cells isolated from high- and low-metastatic tumors. Am J Pathol. 2012;180(3):1294–307. https://doi.org/10.1016/j.ajpath.2011.11.035.

    Article  CAS  PubMed  Google Scholar 

  61. Branco-Price C, et al. Endothelial cell HIF-1α and HIF-2α differentially regulate metastatic success. Cancer Cell. 2012;21(1):52–65. https://doi.org/10.1016/j.ccr.2011.11.017.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Buckanovich RJ, et al. Tumor vascular proteins as biomarkers in ovarian cancer. J Clin Oncol. 2007;25(7):852–61. https://doi.org/10.1200/JCO.2006.08.8583.

    Article  CAS  PubMed  Google Scholar 

  63. St. Croix B, et al. Genes expressed in human tumor endothelium. Science. 2000;289(5482):1197–202. https://doi.org/10.1126/science.289.5482.1197.

    Article  CAS  PubMed  Google Scholar 

  64. Dieterich LC, et al. Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization. J Pathol. 2012;228(3):378–90. https://doi.org/10.1002/path.4072.

    Article  CAS  PubMed  Google Scholar 

  65. Roudnicky F, et al. Endocan is upregulated on tumor vessels in invasive bladder cancer where it mediates VEGF-A-induced angiogenesis. Cancer Res. 2013;73(3):1097–106. https://doi.org/10.1158/0008-5472.CAN-12-1855.

    Article  CAS  PubMed  Google Scholar 

  66. Zhang L, et al. Tumor-derived vascular endothelial growth factor up-regulates angiopoietin-2 in host endothelium and destabilizes host vasculature, supporting angiogenesis in ovarian cancer. Cancer Res. 2003;63(12):3403–12.

    CAS  PubMed  Google Scholar 

  67. Zhao Q, et al. Single-cell transcriptome analyses reveal endothelial cell heterogeneity in tumors and changes following antiangiogenic treatment. Cancer Res. 2018;78(9):2370–82. https://doi.org/10.1158/0008-5472.CAN-17-2728.

    Article  CAS  PubMed  Google Scholar 

  68. Goveia J, et al. An integrated gene expression landscape profiling approach to identify lung tumor endothelial cell heterogeneity and angiogenic candidates. Cancer Cell. 2020;37(1):21–36.e13. https://doi.org/10.1016/j.ccell.2019.12.001.

    Article  CAS  PubMed  Google Scholar 

  69. Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: causes, consequences, challenges and opportunities. Cell Mol Life Sci. 2020;77(9):1745–70. https://doi.org/10.1007/s00018-019-03351-7.

    Article  CAS  PubMed  Google Scholar 

  70. Hwa C, Sebastian A, Aird WC. Endothelial biomedicine: its status as an interdisciplinary field, its progress as a basic science, and its translational bench-to-bedside gap. Endothelium. 2005;12(3):139–51. https://doi.org/10.1080/10623320500192016.

    Article  CAS  PubMed  Google Scholar 

  71. Kahn BM, et al. The vascular landscape of human cancer. J Clin Invest. 2021;131(2):e136655. https://doi.org/10.1172/JCI136655.

    Article  CAS  PubMed Central  Google Scholar 

  72. Mezheyeuski A, et al. Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer. Oncotarget. 2016;7(27):41948–58. https://doi.org/10.18632/oncotarget.9632.

    Article  PubMed Central  PubMed  Google Scholar 

  73. Asahara T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7. https://doi.org/10.1126/science.275.5302.964.

    Article  CAS  PubMed  Google Scholar 

  74. Yin AH, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997;90(12):5002–12. https://doi.org/10.1182/blood.v90.12.5002.

    Article  CAS  PubMed  Google Scholar 

  75. Peichev M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors. Blood. 2000;95(3):952–8. https://doi.org/10.1182/blood.v95.3.952.003k27_952_958.

    Article  CAS  PubMed  Google Scholar 

  76. Romagnani P, et al. CD14+CD34low cells with stem cell phenotypic and functional features are the major source of circulating endothelial progenitors. Circ Res. 2005;97(4):314–22. https://doi.org/10.1161/01.RES.0000177670.72216.9b.

    Article  CAS  PubMed  Google Scholar 

  77. Asahara T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999a;85(3):221–8. https://doi.org/10.1161/01.RES.85.3.221.

    Article  CAS  PubMed  Google Scholar 

  78. Asahara T, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999b;18(14):3964–72. https://doi.org/10.1093/emboj/18.14.3964.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Kalka C, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci. 2000;97(7):3422–7. https://doi.org/10.1073/pnas.97.7.3422.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Lin Y, et al. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Investig. 2000;105(1):71–7. https://doi.org/10.1172/JCI8071.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Shi Q, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood. 1998;92(2):362–7. https://doi.org/10.1182/blood.v92.2.362.

    Article  CAS  PubMed  Google Scholar 

  82. Shin JW, et al. Isolation of endothelial progenitor cells from cord blood and induction of differentiation by Ex Vivo expansion. Yonsei Med J. 2005;46(2):260–7. https://doi.org/10.3349/ymj.2005.46.2.260.

    Article  PubMed Central  PubMed  Google Scholar 

  83. Blann AD, et al. Circulating endothelial cells. Biomarker of vascular disease. Thromb Haemost. 2005;93(2):228–35. https://doi.org/10.1160/TH04-09-0578.

    Article  CAS  PubMed  Google Scholar 

  84. Bertolini F, et al. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer. 2006;6(11):835–45. https://doi.org/10.1038/nrc1971.

    Article  CAS  PubMed  Google Scholar 

  85. Ronzoni M, et al. Circulating endothelial cells and endothelial progenitors as predictive markers of clinical response to bevacizumab-based first-line treatment in advanced colorectal cancer patients. Ann Oncol. 2010;21(12):2382–9. https://doi.org/10.1093/annonc/mdq261.

    Article  CAS  PubMed  Google Scholar 

  86. Mehran R, et al. Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy. Cancer Res. 2014;74(10):2731–41. https://doi.org/10.1158/0008-5472.CAN-13-2044.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Cima I, et al. Tumor-derived circulating endothelial cell clusters in colorectal cancer. Sci Transl Med. 2016;8(345):345ra89. https://doi.org/10.1126/scitranslmed.aad7369.

    Article  CAS  PubMed  Google Scholar 

  88. Rahbari NN, et al. Prognostic value of circulating endothelial cells in metastatic colorectal cancer. Oncotarget. 2017;8(23):37491–501. https://doi.org/10.18632/oncotarget.16397.

    Article  PubMed Central  PubMed  Google Scholar 

  89. Andonegui-Elguera MA, et al. An overview of vasculogenic mimicry in breast cancer. Front Oncol. 2020;10(February):1–8. https://doi.org/10.3389/fonc.2020.00220.

    Article  Google Scholar 

  90. Lizárraga-Verdugo E, et al. Cancer stem cells and its role in angiogenesis and vasculogenic mimicry in gastrointestinal cancers. Front Oncol. 2020;10(March):1–8. https://doi.org/10.3389/fonc.2020.00413.

    Article  Google Scholar 

  91. Luo Q, et al. Vasculogenic mimicry in carcinogenesis and clinical applications. J Hematol Oncol. 2020;13(1):1–15. https://doi.org/10.1186/s13045-020-00858-6.

    Article  Google Scholar 

  92. Maniotis AJ, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol. 1999;155(3):739–52. https://doi.org/10.1016/S0002-9440(10)65173-5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Álvarez-Viejo M, et al. CD271 as a marker to identify mesenchymal stem cells from diverse sources before culture. World J Stem Cells. 2015;7(2):470–6. https://doi.org/10.4252/wjsc.v7.i2.470.

    Article  PubMed Central  PubMed  Google Scholar 

  94. Delgado-Bellido D, et al. VE-cadherin promotes vasculogenic mimicry by modulating kaiso-dependent gene expression. Cell Death Differ. 2019;26(2):348–61. https://doi.org/10.1038/s41418-018-0125-4.

    Article  CAS  PubMed  Google Scholar 

  95. Cao Z, et al. Tumour vasculogenic mimicry is associated with poor prognosis of human cancer patients: a systemic review and meta-analysis. Eur J Cancer. 2013b;49(18):3914–23. https://doi.org/10.1016/j.ejca.2013.07.148.

    Article  PubMed  Google Scholar 

  96. Yang JP, et al. Tumor vasculogenic mimicry predicts poor prognosis in cancer patients: a meta-analysis. Angiogenesis. 2016;19(2):191–200. https://doi.org/10.1007/s10456-016-9500-2.

    Article  CAS  PubMed  Google Scholar 

  97. Shen Y, et al. Tumor vasculogenic mimicry formation as an unfavorable prognostic indicator in patients with breast cancer. Oncotarget. 2017;8(34):56408–16. https://doi.org/10.18632/oncotarget.16919.

    Article  PubMed Central  PubMed  Google Scholar 

  98. Zhang Z, et al. The role of vascular mimicry as a biomarker in malignant melanoma: a systematic review and meta-analysis. BMC Cancer. 2019;19(1):1–12. https://doi.org/10.1186/s12885-019-6350-5.

    Article  CAS  Google Scholar 

  99. Alvero AB, et al. Stem-like ovarian cancer cells can serve as tumor vascular progenitors. Stem Cells. 2009;27(10):2405–13. https://doi.org/10.5949/liverpool/9780853236788.003.0003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Bussolati B, et al. Endothelial cell differentiation of human breast tumour stem/progenitor cells. J Cell Mol Med. 2009;13(2):309–19. https://doi.org/10.1111/j.1582-4934.2008.00338.x.

    Article  CAS  PubMed  Google Scholar 

  101. Li F, Xu J, Liu S. Cancer stem cells and neovascularization. Cells. 2021;10(5):1070. https://doi.org/10.3390/cells10051070.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  102. Mei X, et al. Glioblastoma stem cell differentiation into endothelial cells evidenced through live-cell imaging. Neuro-Oncology. 2017;19(8):1109–18. https://doi.org/10.1093/neuonc/nox016.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  103. Wang R, et al. Glioblastoma stem-like cells give rise to tumour endothelium. Nature. 2010;468(7325):829–33. https://doi.org/10.1038/nature09624.

    Article  CAS  PubMed  Google Scholar 

  104. Ricci-Vitiani L, et al. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature. 2010;468(7325):824–30. https://doi.org/10.1038/nature09557.

    Article  CAS  PubMed  Google Scholar 

  105. Zhao Y, et al. Endothelial cell transdifferentiation of human glioma stem progenitor cells in vitro. Brain Res Bull. 2010;82(5–6):308–12. https://doi.org/10.1016/j.brainresbull.2010.06.006.

    Article  CAS  PubMed  Google Scholar 

  106. Bussolati B, et al. Identification of a tumor-initiating stem cell population in human renal carcinomas. FASEB J. 2008;22(10):3696–705. https://doi.org/10.1096/fj.08-102590.

    Article  CAS  PubMed  Google Scholar 

  107. Rau K-M, et al. Neovascularization evaluated by CD105 correlates well with prognostic factors in breast cancers. Exp Ther Med. 2012;4(2):231–6. https://doi.org/10.3892/etm.2012.594.

    Article  PubMed Central  PubMed  Google Scholar 

  108. Saroufim A, et al. Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma. Br J Cancer. 2014;110(7):1778–84. https://doi.org/10.1038/bjc.2014.71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Aomatsu N, et al. CD133 is a useful surrogate marker for predicting chemosensitivity to neoadjuvant chemotherapy in breast cancer. PLoS One. 2012;7(9):e45865. https://doi.org/10.1371/journal.pone.0045865.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  110. Kim SJ, et al. Prognostic impact and clinicopathological correlation of CD133 and ALDH1 expression in invasive breast cancer. J Breast Cancer. 2015;18(4):347–55. https://doi.org/10.4048/jbc.2015.18.4.347.

    Article  PubMed Central  PubMed  Google Scholar 

  111. Rettig WJ, et al. Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer. Proc Natl Acad Sci U S A. 1992;89(22):10832–6. https://doi.org/10.1073/pnas.89.22.10832.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  112. Chang SS, et al. Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clinical Cancer Res. 1999;5(10):2674–81.

    CAS  Google Scholar 

  113. Abid MR, et al. Vascular endocan is preferentially expressed in tumor endothelium. Microvasc Res. 2006;72(3):136–45. https://doi.org/10.1016/j.mvr.2006.05.010.

    Article  CAS  PubMed  Google Scholar 

  114. Burrows FJ, et al. Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy. Clin Cancer Res. 1995;1(12):1623–34.

    CAS  PubMed  Google Scholar 

  115. Gasparini G, et al. Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. Clin Res. 1998;4(11):2625–34.

    CAS  Google Scholar 

  116. Kim S, et al. Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin. Am J Pathol. 2000;156(4):1345–62. https://doi.org/10.1016/s0002-9440(10)65005-5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  117. Griffioen AW, et al. Endothelial intercellular adhesion molecule-1 expression is suppressed in human malignancies: the role of angiogenic factors. Cancer Res. 1996;56(5):1111–7.

    CAS  PubMed  Google Scholar 

  118. Hellwig SMM, et al. Endothelial CD34 is suppressed in human malignancies: role of angiogenic factors. Cancer Lett. 1997;120(2):203–11. https://doi.org/10.1016/S0304-3835(97)00310-8.

    Article  CAS  PubMed  Google Scholar 

  119. Davies G, et al. Levels of expression of endothelial markers specific to tumour-associated endothelial cells and their correlation with prognosis in patients with breast cancer. Clin Exp Metastasis. 2004;21(1):31–7. https://doi.org/10.1023/b:clin.0000017168.83616.d0.

    Article  CAS  PubMed  Google Scholar 

  120. Rmali KA, et al. Tumour endothelial marker 8 (TEM-8) in human colon cancer and its association with tumour progression. Eur J Surg Oncol. 2004;30(9):948–53. https://doi.org/10.1016/j.ejso.2004.07.023.

    Article  CAS  PubMed  Google Scholar 

  121. Rmali KA, Puntis MCA, Jiang WG. Prognostic values of tumor endothelial markers in patients with colorectal cancer. World J Gastroenterol. 2005;11(9):1283–6. https://doi.org/10.3748/wjg.v11.i9.1283.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  122. Fuchs B, et al. High expression of tumor endothelial marker 7 is associated with metastasis and poor survival of patients with osteogenic sarcoma. Gene. 2007;399(2):137–43. https://doi.org/10.1016/j.gene.2007.05.003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  123. MacFadyen J, et al. Endosialin is expressed on stromal fibroblasts and CNS pericytes in mouse embryos and is downregulated during development. Gene Expr Patterns. 2007;7(3):363–9. https://doi.org/10.1016/j.modgep.2006.07.006.

    Article  CAS  PubMed  Google Scholar 

  124. Opavsky R, et al. Molecular characterization of the mouse Tem1/endosialin gene regulated by cell density in vitro and expressed in normal tissues in vivo. J Biol Chem. 2001;276(42):38795–807. https://doi.org/10.1074/jbc.M105241200.

    Article  CAS  PubMed  Google Scholar 

  125. Halder C, et al. Preferential expression of the secreted and membrane forms of tumor endothelial marker 7 transcripts in osteosarcoma. Anticancer Res. 2009;29(11):4317–22.

    CAS  PubMed Central  PubMed  Google Scholar 

  126. Lee HK, et al. Cloning, characterization and neuronal expression profiles of tumor endothelial marker 7 in the rat brain. Brain Res Mol Brain Res. 2005a;136(1–2):189–98. https://doi.org/10.1016/j.molbrainres.2005.02.010.

    Article  CAS  PubMed  Google Scholar 

  127. Zhang ZZ, et al. TEM7 (PLXDC1), a key prognostic predictor for resectable gastric cancer, promotes cancer cell migration and invasion. Am J Cancer Res. 2015;5(2):772–81.

    PubMed Central  PubMed  Google Scholar 

  128. Czekierdowski A, et al. Prognostic significance of TEM7 and nestin expression in women with advanced high grade serous ovarian cancer. Ginekol Pol. 2018;89(3):135–41. https://doi.org/10.5603/GP.a2018.0023.

    Article  PubMed  Google Scholar 

  129. Gutwein LG, et al. Tumor endothelial marker 8 expression in triple-negative breast cancer. Anticancer Res. 2011;31(10):3417–22. Available at: https://ar.iiarjournals.org/content/31/10/3417

    CAS  PubMed  Google Scholar 

  130. Kuo F, et al. Immuno-PET imaging of tumor endothelial Marker 8 (TEM8). Mol Pharm. 2014;11(11):3996–4006. https://doi.org/10.1021/mp500056d.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  131. Pietrzyk Ł, et al. Clinical value of detecting tumor endothelial marker 8 (Antxr1) as a biomarker in the diagnosis and prognosis of colorectal cancer. Cancer Manag Res. 2021;13:3113–22. https://doi.org/10.2147/CMAR.S298165.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  132. Basilio-de-Oliveira RP, Pannain VLN. Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors. World J Gastroenterol. 2015;21(22):6924–30. https://doi.org/10.3748/wjg.v21.i22.6924.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  133. Salvesen HB, et al. Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas. APMIS. 2003;111(11):1011–8. https://doi.org/10.1111/j.1600-0463.2003.apm1111103.x.

    Article  PubMed  Google Scholar 

  134. Straume O, Akslen LA. Expression of vascular endothelial growth factor, its receptors (FLT-1, KDR) and TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas. Am J Pathol. 2001;159(1):223–35. https://doi.org/10.1016/S0002-9440(10)61688-4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  135. Svatek RS, et al. Preoperative plasma endoglin levels predict biochemical progression after radical prostatectomy. Clin Cancer Res. 2008;14(11):3362–6. https://doi.org/10.1158/1078-0432.CCR-07-4707.

    Article  CAS  PubMed  Google Scholar 

  136. Östman A, Corvigno S. Microvascular mural cells in cancer. Trends Cancer. 2018;4(12):838–48. https://doi.org/10.1016/j.trecan.2018.10.004.

    Article  CAS  PubMed  Google Scholar 

  137. Sinha D, et al. Pericytes promote malignant ovarian cancer progression in mice and predict poor prognosis in serous ovarian cancer patients. Clin Cancer Res. 2016;22(7):1813–24. https://doi.org/10.1158/1078-0432.CCR-15-1931.

    Article  CAS  PubMed  Google Scholar 

  138. Viski C, et al. Endosialin-expressing pericytes promote metastatic dissemination. Cancer Res. 2016;76(18):5313–25. https://doi.org/10.1158/0008-5472.CAN-16-0932.

    Article  CAS  PubMed  Google Scholar 

  139. Cantelmo AR, et al. Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy. Cancer Cell. 2016;30(6):968–85. https://doi.org/10.1016/j.ccell.2016.10.006.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  140. Cooke VG, et al. Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer cell. 2012;21(1):66–81. https://doi.org/10.1016/j.ccr.2011.11.024.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  141. Hamzah J, et al. Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature. 2008;453(7193):410–4. https://doi.org/10.1038/nature06868.

    Article  CAS  PubMed  Google Scholar 

  142. Hong J, et al. Role of tumor pericytes in the recruitment of myeloid-derived suppressor cells. J Natl Cancer Inst. 2015;107(10):djv209. https://doi.org/10.1093/jnci/djv209.

    Article  CAS  PubMed  Google Scholar 

  143. Lyle LT, et al. Alterations in pericyte subpopulations are associated with elevated blood-tumor barrier permeability in experimental brain metastasis of breast cancer. Clin Cancer Res. 2016;22(21):5287–99. https://doi.org/10.1158/1078-0432.CCR-15-1836.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  144. Nisancioglu MH, Betsholtz C, Genové G. The absence of pericytes does not increase the sensitivity of tumor vasculature to vascular endothelial growth factor-A blockade. Cancer Res. 2010;70(12):5109–15. https://doi.org/10.1158/0008-5472.CAN-09-4245.

    Article  CAS  PubMed  Google Scholar 

  145. Xian X, et al. Pericytes limit tumor cell metastasis. J Clin Invest. 2006;116(3):642–51. https://doi.org/10.1172/JCI25705.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  146. Cao Y, et al. Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma. Cancer. 2013a;119(2):313–24. https://doi.org/10.1002/cncr.27746.

    Article  CAS  PubMed  Google Scholar 

  147. Corvigno S, et al. Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: inter- and intra-patient heterogeneity and impact on survival. Oncotarget. 2016;7(14):18573–84. https://doi.org/10.18632/oncotarget.7613.

    Article  PubMed Central  PubMed  Google Scholar 

  148. Frödin M, et al. Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma. Br J Cancer. 2017;116(2):195–201. https://doi.org/10.1038/bjc.2016.407.

    Article  CAS  PubMed  Google Scholar 

  149. Tolaney SM, et al. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients. Proc Natl Acad Sci U S A. 2015;112(46):14325–30. https://doi.org/10.1073/pnas.1518808112.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  150. Zhou W, et al. Targeting glioma stem cell-derived pericytes disrupts the blood-tumor barrier and improves chemotherapeutic efficacy. Cell Stem Cell. 2017;21(5):591–603.e4. https://doi.org/10.1016/j.stem.2017.10.002.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  151. Bhati R, et al. Molecular characterization of human breast tumor vascular cells. Am J Pathol. 2008;172(5):1381–90. https://doi.org/10.2353/ajpath.2008.070988.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  152. Madden SL, et al. Vascular gene expression in nonneoplastic and malignant brain. Am J Pathol. 2004;165(2):601–8. https://doi.org/10.1016/s0002-9440(10)63324-x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  153. Parker BS, et al. Alterations in vascular gene expression in invasive breast carcinoma. Cancer Res. 2004;64(21):7857–66. https://doi.org/10.1158/0008-5472.CAN-04-1976.

    Article  CAS  PubMed  Google Scholar 

  154. Pen A, et al. Molecular markers of extracellular matrix remodeling in glioblastoma vessels: microarray study of laser-captured glioblastoma vessels. Glia. 2007;55(6):559–72. https://doi.org/10.1002/glia.20481.

    Article  PubMed  Google Scholar 

  155. Dudley AC. Tumor endothelial cells. Cold Spring Harb Perspect Med. 2012;2(3):1–18. https://doi.org/10.1101/cshperspect.a006536.

    Article  CAS  Google Scholar 

  156. Carson-Walter EB, et al. Plasmalemmal vesicle associated protein-1 is a novel marker implicated in brain tumor angiogenesis. Clinical Cancer Res. 2005;11(21):7643–50. https://doi.org/10.1158/1078-0432.CCR-05-1099.

    Article  CAS  Google Scholar 

  157. van Beijnum JR, et al. Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature. Blood. 2006;108(7):2339–48. https://doi.org/10.1182/blood-2006-02-004291.

    Article  CAS  PubMed  Google Scholar 

  158. Hoda MA, et al. Temsirolimus inhibits malignant pleural mesothelioma growth in vitro and in vivo: synergism with chemotherapy. J Thorac Oncol. 2011;6(5):852–63. https://doi.org/10.1097/JTO.0b013e31820e1a25.

    Article  PubMed  Google Scholar 

  159. Lu C, et al. Gene alterations identified by expression profiling in tumor-associated endothelial cells from invasive ovarian carcinoma. Cancer Res. 2007;67(4):1757–68. https://doi.org/10.1158/0008-5472.CAN-06-3700.

    Article  CAS  PubMed  Google Scholar 

  160. Coppiello G, et al. Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake. Circulation. 2015;131(9):815–26. https://doi.org/10.1161/CIRCULATIONAHA.114.013721.

    Article  CAS  PubMed  Google Scholar 

  161. Marcu R, et al. Human organ-specific endothelial cell heterogeneity. iScience. 2018;4:20–35. https://doi.org/10.1016/j.isci.2018.05.003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  162. Nolan DJ, et al. Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell. 2013;26(2):204–19. https://doi.org/10.1016/j.devcel.2013.06.017.Molecular.

    Article  CAS  PubMed  Google Scholar 

  163. Sabbagh MF, et al. Transcriptional and epigenomic landscapes of CNS and non-CNS vascular endothelial cells. eLife. 2018;7:e36187. https://doi.org/10.7554/eLife.36187.

    Article  PubMed Central  PubMed  Google Scholar 

  164. Tewari KS, et al. Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. J Clin Oncol. 2019;37(26):2317–28. https://doi.org/10.1200/JCO.19.01009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  165. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182–6. https://doi.org/10.1056/NEJM197111182852108.

    Article  CAS  PubMed  Google Scholar 

  166. Cao Y, et al. Forty-year journey of angiogenesis translational research. Sci Transl Med. 2011;3(114):114rv3. https://doi.org/10.1126/scitranslmed.3003149.

    Article  PubMed Central  PubMed  Google Scholar 

  167. Folkman J, et al. Isolation of a tumor factor responsible for angiogenesis. J Exp Med. 1971;133(2):275–88. https://doi.org/10.1084/jem.133.2.275.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  168. Viloria-Petit A, et al. Contrasting effects of VEGF gene disruption in embryonic stem cell-derived versus oncogene-induced tumors. EMBO J. 2003;22(16):4091–102. https://doi.org/10.1093/emboj/cdg408.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  169. Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell. 2019;176(6):1248–64. https://doi.org/10.1016/j.cell.2019.01.021.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  170. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25(4):581–611. https://doi.org/10.1210/er.2003-0027.

    Article  CAS  PubMed  Google Scholar 

  171. Jiang BH, Liu LZ. Chapter 2 PI3K/PTEN signaling in angiogenesis and tumorigenesis. Adv Cancer Res. 2009;102(09):19–65. https://doi.org/10.1016/S0065-230X(09)02002-8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  172. Takahashi T, et al. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-γ and DNA synthesis in vascular endothelial cells. EMBO J. 2001;20(11):2768–78. https://doi.org/10.1093/emboj/20.11.2768.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  173. van Hinsbergh VWM, Koolwijk P. Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead. Cardiovasc Res. 2008;78(2):203–12. https://doi.org/10.1093/cvr/cvm102.

    Article  CAS  PubMed  Google Scholar 

  174. Weis S, et al. Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol. 2004;167(2):223–9. https://doi.org/10.1083/jcb.200408130.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  175. Niu G, Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr Drug Targets. 2010;11(8):1000–17. https://doi.org/10.2174/138945010791591395.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  176. Bell C, et al. Oligonucleotide NX1838 inhibits VEGF165-mediated cellular responses in vitro. In Vitro cell Dev Biol Anim. 1999;35(9):533–42. https://doi.org/10.1007/s11626-999-0064-y.

    Article  CAS  PubMed  Google Scholar 

  177. Lee JH, et al. A therapeutic aptamer inhibits angiogenesis by specifically targeting the heparin binding domain of VEGF165. Proc Natl Acad Sci. 2005b;102(52):18902–7. https://doi.org/10.1073/pnas.0509069102.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  178. Lin YS, et al. Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor. J Pharmacol Exp Ther. 1999;288(1):371–8.

    CAS  PubMed  Google Scholar 

  179. Lockhart AC, et al. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol. 2010;28(2):207–14. https://doi.org/10.1200/JCO.2009.22.9237.

    Article  CAS  PubMed  Google Scholar 

  180. Zhou B, Wang B. Pegaptanib for the treatment of age-related macular degeneration. Exp Eye Res. 2006;83(3):615–9. https://doi.org/10.1016/j.exer.2006.02.010.

    Article  CAS  PubMed  Google Scholar 

  181. Spratlin JL, et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010;28(5):780–7. https://doi.org/10.1200/JCO.2009.23.7537.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  182. Faivre S, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24(1):25–35. https://doi.org/10.1200/JCO.2005.02.2194.

    Article  CAS  PubMed  Google Scholar 

  183. Hutson TE, et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010;28(3):475–80. https://doi.org/10.1200/JCO.2008.21.6994.

    Article  CAS  PubMed  Google Scholar 

  184. Iwamoto FM, et al. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro-Oncology. 2010;12(8):855–61. https://doi.org/10.1093/neuonc/noq025.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  185. Sloan B, Scheinfeld NS. Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy. Curr Opin Investig Drugs. 2008;9(12):1324–35.

    CAS  PubMed  Google Scholar 

  186. Strumberg D, et al. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol. 2005;23(5):965–72. https://doi.org/10.1200/JCO.2005.06.124.

    Article  CAS  PubMed  Google Scholar 

  187. Wilhelm SM, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64(19):7099–109. https://doi.org/10.1158/0008-5472.CAN-04-1443.

    Article  CAS  PubMed  Google Scholar 

  188. Zirlik K, Duyster J. Anti-angiogenics: current situation and future perspectives. Oncol Res Treat. 2018;41(4):166–71. https://doi.org/10.1159/000488087.

    Article  CAS  PubMed  Google Scholar 

  189. Jimenez-Pascual A, et al. FGF2: a novel druggable target for glioblastoma? Expert Opin Ther Targets. 2020;24(4):311–8. https://doi.org/10.1080/14728222.2020.1736558.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  190. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10(2):116–29. https://doi.org/10.1038/nrc2780.

    Article  CAS  PubMed  Google Scholar 

  191. Yu P, et al. FGF-dependent metabolic control of vascular development. Nature. 2017;545(7653):224–8. https://doi.org/10.1038/nature22322.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  192. Incio J, et al. Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2. Sci Transl Med. 2018;10(432):eaag0945. https://doi.org/10.1126/scitranslmed.aag0945.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  193. Brady N, et al. The FGF/FGFR axis as a therapeutic target in breast cancer. Expert Rev Endocrinol Metab. 2013;8(4):391–402. https://doi.org/10.1586/17446651.2013.811910.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  194. Jain VK, Turner NC. Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer. Breast Cancer Res. 2012;14(3):208. https://doi.org/10.1186/bcr3139.

    Article  PubMed Central  PubMed  Google Scholar 

  195. Kloepper J, et al. Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival. Proc Natl Acad Sci U S A. 2016;113(16):4476–81. https://doi.org/10.1073/pnas.1525360113.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  196. Peterson TE, et al. Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages. Proc Natl Acad Sci U S A. 2016;113(16):4470–5. https://doi.org/10.1073/pnas.1525349113.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  197. Adams RH, Klein R. Eph receptors and ephrin ligands. Essential mediators of vascular development. Trends Cardiovasc Med. 2000;10(5):183–8. https://doi.org/10.1016/s1050-1738(00)00046-3.

    Article  CAS  PubMed  Google Scholar 

  198. Holder N, Klein R. Eph receptors and ephrins: effectors of morphogenesis. Development. 1999;126(10):2033–44.

    Article  CAS  PubMed  Google Scholar 

  199. Kullander K, Klein R. Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol. 2002;3(7):475–86. https://doi.org/10.1038/nrm856.

    Article  CAS  PubMed  Google Scholar 

  200. Dodelet VC, Pasquale EB. Eph receptors and ephrin ligands: embryogenesis to tumorigenesis. Oncogene. 2000;19(49):5614–9. https://doi.org/10.1038/sj.onc.1203856.

    Article  CAS  PubMed  Google Scholar 

  201. Ogawa K, et al. The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene. 2000;19(52):6043–52. https://doi.org/10.1038/sj.onc.1204004.

    Article  CAS  PubMed  Google Scholar 

  202. Surawska H, Ma PC, Salgia R. The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev. 2004;15(6):419–33. https://doi.org/10.1016/j.cytogfr.2004.09.002.

    Article  CAS  PubMed  Google Scholar 

  203. Noren NK, et al. Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Proc Natl Acad Sci U S A. 2004;101(15):5583–8. https://doi.org/10.1073/pnas.0401381101.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  204. Uhl C, et al. EphB4 mediates resistance to antiangiogenic therapy in experimental glioma. Angiogenesis. 2018;21(4):873–81. https://doi.org/10.1007/s10456-018-9633-6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  205. Krusche B, et al. EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells. elife. 2016;5:1–32. https://doi.org/10.7554/elife.14845.

    Article  CAS  Google Scholar 

  206. Brantley DM, et al. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene. 2002;21(46):7011–26. https://doi.org/10.1038/sj.onc.1205679.

    Article  CAS  PubMed  Google Scholar 

  207. Cheng N, et al. Inhibition of VEGF-dependent multistage carcinogenesis by soluble EphA receptors. Neoplasia. 2003;5(5):445–56. https://doi.org/10.1016/s1476-5586(03)80047-7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  208. Dobrzanski P, et al. Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist. Cancer Res. 2004;64(3):910–9. https://doi.org/10.1158/0008-5472.can-3430-2.

    Article  CAS  PubMed  Google Scholar 

  209. Berta J, et al. Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis. J Thorac Oncol. 2010;5(8):1120–9. https://doi.org/10.1097/JTO.0b013e3181e2c1ff.

    Article  PubMed  Google Scholar 

  210. Feng M, et al. Tumor apelin, not serum apelin, is associated with the clinical features and prognosis of gastric cancer. BMC Cancer. 2016;16(1):1–8. https://doi.org/10.1186/s12885-016-2815-y.

    Article  CAS  Google Scholar 

  211. Heo K, et al. Hypoxia-induced up-regulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients. Oral Oncol. 2012;48(6):500–6. https://doi.org/10.1016/j.oraloncology.2011.12.015.

    Article  CAS  PubMed  Google Scholar 

  212. Kälin RE, et al. Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis. Dev Biol. 2007;305(2):599–614. https://doi.org/10.1016/j.ydbio.2007.03.004.

    Article  CAS  PubMed  Google Scholar 

  213. Lacquaniti A, et al. Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation. Clin Exp Med. 2015;15(1):97–105. https://doi.org/10.1007/s10238-014-0272-y.

    Article  CAS  PubMed  Google Scholar 

  214. Seaman S, et al. Genes that distinguish physiological and pathological angiogenesis. Cancer Cell. 2007;11(6):539–54. https://doi.org/10.1016/j.ccr.2007.04.017.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  215. Tolkach Y, et al. Apelin and apelin receptor expression in renal cell carcinoma. Br J Cancer. 2019;120(6):633–9. https://doi.org/10.1038/s41416-019-0396-7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  216. Wysocka MB, Pietraszek-Gremplewicz K, Nowak D. The role of apelin in cardiovascular diseases, obesity and cancer. Front Physiol. 2018;9:557. https://doi.org/10.3389/fphys.2018.00557.

    Article  PubMed Central  PubMed  Google Scholar 

  217. Berta J, et al. Apelin promotes lymphangiogenesis and lymph node metastasis. Oncotarget. 2014;5(12):4426–37. https://doi.org/10.18632/oncotarget.2032.

    Article  PubMed Central  PubMed  Google Scholar 

  218. Hall C, et al. Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth. Cancer Lett. 2017;386:179–88. https://doi.org/10.1016/j.canlet.2016.11.025.

    Article  CAS  PubMed  Google Scholar 

  219. Lv D, et al. PAK1-cofilin phosphorylation mediates human lung adenocarcinoma cells migration induced by apelin-13. Clin Exp Pharmacol Physiol. 2016;43(5):569–79. https://doi.org/10.1111/1440-1681.12563.

    Article  CAS  PubMed  Google Scholar 

  220. Macaluso NJM, et al. Discovery of a competitive apelin receptor (APJ) antagonist. ChemMedChem. 2011;6(6):1017–23. https://doi.org/10.1002/cmdc.201100069.

    Article  CAS  PubMed  Google Scholar 

  221. Harford-Wright E, et al. Pharmacological targeting of apelin impairs glioblastoma growth. Brain. 2017;140(11):2939–54. https://doi.org/10.1093/brain/awx253.

    Article  PubMed Central  PubMed  Google Scholar 

  222. Mastrella G, et al. Targeting APLN/APLNR improves antiangiogenic efficiency and blunts proinvasive side effects of VEGFA/VEGFR2 blockade in glioblastoma. Cancer Res. 2019;79(9):2298–313. https://doi.org/10.1158/0008-5472.CAN-18-0881.

    Article  CAS  PubMed  Google Scholar 

  223. Uribesalgo I, et al. Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy. EMBO Mol Med. 2019;11(8):e9266. https://doi.org/10.15252/emmm.201809266.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  224. Chae S, et al. Angiopoietin-2 interferes with anti-VEGFR2- induced vessel normalization and survival benefit in mice bearing gliomas. Clin Cancer Res. 2010;16(14):3618–27. https://doi.org/10.1158/1078-0432.CCR-09-3073.Angiopoietin-2.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  225. Shim WSN, Ho IAW, Wong PEH. Angiopoietin: a TIE(d) balance in tumor angiogenesis. Mol Cancer Res. 2007;5(7):655–65. https://doi.org/10.1158/1541-7786.MCR-07-0072.

    Article  CAS  PubMed  Google Scholar 

  226. Ping YF, Bian XW. Consice review: contribution of cancer stem cells to neovascularization. Stem Cells. 2011;29(6):888–94. https://doi.org/10.1002/stem.650.

    Article  CAS  PubMed  Google Scholar 

  227. Bach P, et al. Specific elimination of CD133+ tumor cells with targeted oncolytic measles virus. Cancer Res. 2013;73(2):865–74. https://doi.org/10.1158/0008-5472.CAN-12-2221.

    Article  CAS  PubMed  Google Scholar 

  228. Xu MR, et al. Brucine suppresses vasculogenic mimicry in human triple-negative breast cancer cell line MDA-MB-231. In: W.-L. Lu, Editor. Biomed Res Int. 2019;2019:6543230. https://doi.org/10.1155/2019/6543230.

  229. Serwe A, et al. Inhibition of TGF-β signaling, vasculogenic mimicry and proinflammatory gene expression by isoxanthohumol. Investig New Drugs. 2012;30(3):898–915. https://doi.org/10.1007/s10637-011-9643-3.

    Article  CAS  Google Scholar 

  230. Kumar SR, et al. Molecular targets for tivantinib (ARQ 197) and vasculogenic mimicry in human melanoma cells. Eur J Pharmacol. 2019;853:316–24. https://doi.org/10.1016/j.ejphar.2019.04.010.

    Article  CAS  PubMed  Google Scholar 

  231. Fernández-Cortés M, Delgado-Bellido D, Javier Oliver F. Vasculogenic mimicry: become an endothelial cell “But not so much”. Front Oncol. 2019;9(AUG):1–6. https://doi.org/10.3389/fonc.2019.00803.

    Article  Google Scholar 

  232. Jean C, et al. Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function. J Cell Biol. 2014;204(2):247–63. https://doi.org/10.1083/jcb.201307067.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  233. Goel S, et al. Effects of vascular-endothelial protein tyrosine phosphatase inhibition on breast cancer vasculature and metastatic progression. J Natl Cancer Inst. 2013;105(16):1188–201. https://doi.org/10.1093/jnci/djt164.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  234. George D. Platelet-derived growth factor receptors: a therapeutic target in solid tumors. Semin Oncol. 2001;28:27–33. https://doi.org/10.1016/S0093-7754(01)90100-9.

    Article  CAS  PubMed  Google Scholar 

  235. Thijssen VL, et al. Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth. J Pathol. 2018;246(4):447–58. https://doi.org/10.1002/path.5152.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  236. Uehara H, et al. Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases. J Natl Cancer Inst. 2003;95(6):458–70. https://doi.org/10.1093/jnci/95.6.458.

    Article  CAS  PubMed  Google Scholar 

  237. Heidemann J, et al. Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2. J Biol Chem. 2003;278(10):8508–15. https://doi.org/10.1074/jbc.M208231200.

    Article  CAS  PubMed  Google Scholar 

  238. Kitadai Y, et al. Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8. Clin Cancer Res. 2000;6(7):2735–40.

    CAS  PubMed  Google Scholar 

  239. Yang G, et al. CXCR2 promotes ovarian cancer growth through dysregulated cell cycle, diminished apoptosis, and enhanced angiogenesis. Clin Cancer Res. 2010;16(15):3875–86. https://doi.org/10.1158/1078-0432.CCR-10-0483.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  240. Ijichi H, et al. Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma. J Clin Invest. 2011;121(10):4106–17. https://doi.org/10.1172/JCI42754.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  241. Xu J, et al. Vascular CXCR4 expression promotes vessel sprouting and sensitivity to sorafenib treatment in hepatocellular carcinoma. Clin Cancer Res. 2017;23(15):4482–92. https://doi.org/10.1158/1078-0432.ccr-16-2131.

    Article  CAS  PubMed  Google Scholar 

  242. Chen L, et al. The IL-8/CXCR1 axis is associated with cancer stem cell-like properties and correlates with clinical prognosis in human pancreatic cancer cases. Sci Rep. 2014;4:1–7. https://doi.org/10.1038/srep05911.

    Article  CAS  Google Scholar 

  243. Ha H, Debnath B, Neamati N. Role of the CXCL8-CXCR1/2 axis in cancer and inflammatory diseases. Theranostics. 2017;7(6):1543–88. https://doi.org/10.7150/thno.15625.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  244. Milosevic V, et al. Wnt/IL- 1β/IL -8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5. Int J Cancer. 2020;146(1):192–207. https://doi.org/10.1002/ijc.32419.

    Article  CAS  PubMed  Google Scholar 

  245. Smith DR, et al. Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma. J Exp Med. 1994;179(5):1409–15. https://doi.org/10.1084/jem.179.5.1409.

    Article  CAS  PubMed  Google Scholar 

  246. Martin D, Galisteo R, Gutkind JS. CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex. J Biol Chem. 2009;284(10):6038–42. https://doi.org/10.1074/jbc.C800207200.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  247. Scapini P, et al. CXCL1/macrophage inflammatory protein-2-induced angiogenesis in vivo is mediated by neutrophil-derived vascular endothelial growth factor-A. J Immunol. 2004;172(8):5034–40. https://doi.org/10.4049/jimmunol.172.8.5034.

    Article  CAS  PubMed  Google Scholar 

  248. Wolf MJ, et al. Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway. Cancer Cell. 2012;22(1):91–105. https://doi.org/10.1016/j.ccr.2012.05.023.

    Article  CAS  PubMed  Google Scholar 

  249. Chen X, et al. CCL2/CCR2 regulates the tumor microenvironment in HER-2/neu-driven mammary carcinomas in mice. PLoS One. 2016;11(11):e0165595. https://doi.org/10.1371/journal.pone.0165595.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  250. Oh P, et al. Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy. Nature. 2004;429(6992):629–35. https://doi.org/10.1038/nature02580.

    Article  CAS  PubMed  Google Scholar 

  251. Wei YQ, et al. Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen. Proc Natl Acad Sci U S A. 2001;98(20):11545–50. https://doi.org/10.1073/pnas.191112198.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  252. Gavilondo JV, et al. Specific active immunotherapy with a VEGF vaccine in patients with advanced solid tumors. results of the CENTAURO antigen dose escalation phase I clinical trial. Vaccine. 2014;32(19):2241–50. https://doi.org/10.1016/j.vaccine.2013.11.102.

    Article  CAS  PubMed  Google Scholar 

  253. Chen R, et al. Anti-metastatic effects of DNA vaccine encoding single-chain trimer composed of MHC I and vascular endothelial growth factor receptor 2 peptide. Oncol Rep. 2015;33(5):2269–76. https://doi.org/10.3892/or.2015.3820.

    Article  CAS  PubMed  Google Scholar 

  254. Ishizaki H, et al. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res. 2006;12(19):5841–9. https://doi.org/10.1158/1078-0432.CCR-06-0750.

    Article  CAS  PubMed  Google Scholar 

  255. Liang P, et al. Construction of a DNA vaccine encoding Flk-1 extracellular domain and C3d fusion gene and investigation of its suppressing effect on tumor growth. Cancer Immunol Immunother. 2010;59(1):93–101. https://doi.org/10.1007/s00262-009-0727-2.

    Article  CAS  PubMed  Google Scholar 

  256. Liu JY, et al. Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2. Blood. 2003;102(5):1815–23. https://doi.org/10.1182/blood-2002-12-3772.

    Article  CAS  PubMed  Google Scholar 

  257. McKinney KA, et al. Effect of a novel DNA vaccine on angiogenesis and tumor growth in vivo. Arch Otolaryngol. 2010;136(9):859–64. https://doi.org/10.1001/archoto.2010.139.

    Article  Google Scholar 

  258. Wada S, et al. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 2005;65(11):4939–46. https://doi.org/10.1158/0008-5472.CAN-04-3759.

    Article  CAS  PubMed  Google Scholar 

  259. Xie K, et al. Anti-tumor effects of a human VEGFR-2-based DNA vaccine in mouse models. Genet Vaccines Ther. 2009;7:10. https://doi.org/10.1186/1479-0556-7-10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  260. Zuo SG, et al. Orally administered DNA vaccine delivery by attenuated Salmonella typhimurium targeting fetal liver kinase 1 inhibits murine Lewis lung carcinoma growth and metastasis. Biol Pharm Bull. 2010;33(2):174–82. https://doi.org/10.1248/bpb.33.174.

    Article  CAS  PubMed  Google Scholar 

  261. He Q, et al. Inhibition of tumor growth with a vaccine based on xenogeneic homologous fibroblast growth factor receptor-1 in mice. J Biol Chem. 2003;278(24):21831–6. https://doi.org/10.1074/jbc.M300880200.

    Article  CAS  PubMed  Google Scholar 

  262. Li M, et al. bFGF peptide combined with the pVAX-8CpG plasmid as adjuvant is a novel anticancer vaccine inducing effective immune responses against Lewis lung carcinoma. Mol Med Rep. 2012;5(3):625–30. https://doi.org/10.3892/mmr.2011.725.

    Article  CAS  PubMed  Google Scholar 

  263. Plum SM, et al. Administration of a liposomal FGF-2 peptide vaccine leads to abrogation of FGF-2-mediated angiogenesis and tumor development. Vaccine. 2000;19(9–10):1294–303. https://doi.org/10.1016/s0264-410x(00)00210-3.

    Article  CAS  PubMed  Google Scholar 

  264. Zheng SJ, et al. Synergistic anti-tumor effect of recombinant chicken fibroblast growth factor receptor-1-mediated anti-angiogenesis and low-dose gemcitabine in a mouse colon adenocarcinoma model. World J Gastroenterol. 2007;13(17):2484–9. https://doi.org/10.3748/wjg.v13.i17.2484.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  265. Plum SM, et al. Generation of a specific immunological response to FGF-2 does not affect wound healing or reproduction. Immunopharmacol Immunotoxicol. 2004;26(1):29–41. https://doi.org/10.1081/iph-120029942.

    Article  CAS  PubMed  Google Scholar 

  266. McNeel DG, et al. Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion. Clin Cancer Res. 2005;11(21):7851–60. https://doi.org/10.1158/1078-0432.CCR-05-0262.

    Article  CAS  PubMed  Google Scholar 

  267. Huang FY, et al. Bacterial surface display of endoglin by antigen 43 induces antitumor effectiveness via bypassing immunotolerance and inhibition of angiogenesis. Int J Cancer. 2014;134(8):1981–90. https://doi.org/10.1002/ijc.28511.

    Article  CAS  PubMed  Google Scholar 

  268. Jarosz M, et al. Therapeutic antitumor potential of endoglin-based DNA vaccine combined with immunomodulatory agents. Gene Ther. 2013;20(3):262–73. https://doi.org/10.1038/gt.2012.28.

    Article  CAS  PubMed  Google Scholar 

  269. Fernández Lorente A, et al. Effect of blockade of the EGF system on wound healing in patients vaccinated with CIMAvax® EGF. World J Surg Oncol. 2013;11:275. https://doi.org/10.1186/1477-7819-11-275.

    Article  PubMed Central  PubMed  Google Scholar 

  270. García B, et al. Effective inhibition of the epidermal growth factor/epidermal growth factor receptor binding by anti-epidermal growth factor antibodies is related to better survival in advanced non-small-cell lung cancer patients treated with the epidermal growth factor. Clin Cancer Res. 2008;14(3):840–6. https://doi.org/10.1158/1078-0432.CCR-07-1050.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Medicine, Centre for Cancer Biomarkers CCBIO, University of Bergen, Bergen, Norway

    Vladan Milosevic, Reidunn J. Edelmann, Arne Östman & Lars A. Akslen

  2. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden

    Vladan Milosevic, Reidunn J. Edelmann & Arne Östman

  3. Norwegian Veterinary Institute, Ås, Norway

    Johanna Hol Fosse

Authors
  1. Vladan Milosevic
    View author publications

    Search author on:PubMed Google Scholar

  2. Reidunn J. Edelmann
    View author publications

    Search author on:PubMed Google Scholar

  3. Johanna Hol Fosse
    View author publications

    Search author on:PubMed Google Scholar

  4. Arne Östman
    View author publications

    Search author on:PubMed Google Scholar

  5. Lars A. Akslen
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Vladan Milosevic .

Editor information

Editors and Affiliations

  1. Centre for Cancer Biomarkers CCBIO Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Lars A. Akslen

  2. Department of Surgery, Harvard Medical School, Vascular Biology Program, Boston Children’s Hospital, Boston, USA

    Randolph S. Watnick

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Milosevic, V., Edelmann, R.J., Fosse, J.H., Östman, A., Akslen, L.A. (2022). Molecular Phenotypes of Endothelial Cells in Malignant Tumors. In: Akslen, L.A., Watnick, R.S. (eds) Biomarkers of the Tumor Microenvironment. Springer, Cham. https://doi.org/10.1007/978-3-030-98950-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-98950-7_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-98949-1

  • Online ISBN: 978-3-030-98950-7

  • eBook Packages: MedicineMedicine (R0)

Keywords

Publish with us

Policies and ethics

Profiles

  1. Vladan Milosevic View author profile
  2. Johanna Hol Fosse View author profile
  3. Lars A. Akslen View author profile