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Integrin and Growth Factor Receptor Alliance in Angiogenesis

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Abstract

A sequence of events in vascular and stromal cells maintained in a highly coordinated manner regulates angiogenesis and tissue remodeling. These processes are mediated by the ability of cells to respond to environmental cues and activate surface integrins. Physiological and pathological processes in vascular biology are dependent on the specificity of important signaling mechanisms that are activated through the association between growth factors, their receptors, integrins, and their specific extracellular matrix ligands. A large body of evidence from in vitro and in vivo models demonstrates the importance of coordination of signals from the extracellular environment that activates specific tyrosine kinase receptors and integrins in order to regulate angiogenic processes in vivo. In addition to complex formation between growth factor receptors and integrins, growth factors and cytokines also directly interact with integrins, depending upon their concentration levels in the environment, and differentially regulate integrin-related processes. Recent studies from a number of laboratories including ours have provided important novel insights into the involvement of many signaling events that improve our existing knowledge on the cross-talk between growth factor receptors and integrins in the regulation of angiogenesis. In this review, our focus will be on updating the recent developments in the field of integrin-growth factor receptor associations and their implications in the vascular processes.

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References

  1. Folkman, J. (2007). Angiogenesis: An organizing principle for drug discovery? Nature Reviews. Drug Discovery, 6(4), 273–286.

    PubMed  CAS  Google Scholar 

  2. Folkman, J. (2006). Angiogenesis. Annual Review of Medicine, 57, 1–18.

    PubMed  CAS  Google Scholar 

  3. Gerhardt, H., & Betsholtz, C. (2003). Endothelial-pericyte interactions in angiogenesis. Cell and Tissue Research, 314(1), 15–23.

    PubMed  Google Scholar 

  4. Davis, G. E., & Senger, D. R. (2005). Endothelial extracellular matrix: Biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circulation Research, 97(11), 1093–1107.

    PubMed  CAS  Google Scholar 

  5. Napione, L., Cascone, I., et al. (2007). Integrins: A flexible platform for endothelial vascular tyrosine kinase receptors. Autoimmunity Reviews, 7(1), 18–22.

    PubMed  CAS  Google Scholar 

  6. Rousseau, S., Houle, F., et al. (2000). Integrating the VEGF signals leading to actin-based motility in vascular endothelial cells. Trends in Cardiovascular Medicine, 10(8), 321–327.

    PubMed  CAS  Google Scholar 

  7. Plow, E. F., Haas, T. A., et al. (2000). Ligand binding to integrins. The Journal of Biological Chemistry, 275(29), 21785–21788.

    PubMed  CAS  Google Scholar 

  8. Byzova, T. V., Goldman, C. K., et al. (2002). Adenovirus encoding vascular endothelial growth factor-D induces tissue-specific vascular patterns in vivo. Blood, 99(12), 4434–4442.

    PubMed  CAS  Google Scholar 

  9. Byzova, T. V., Rabbani, R., et al. (1998). Role of integrin alpha(v)beta3 in vascular biology. Thrombosis and Haemostasis, 80(5), 726–734.

    PubMed  CAS  Google Scholar 

  10. Cheresh, D. A. (1991). Structure, function and biological properties of integrin alpha v beta 3 on human melanoma cells. Cancer Metastasis Reviews, 10(1), 3–10.

    PubMed  CAS  Google Scholar 

  11. Brakenhielm, E. (2007). Substrate matters: Reciprocally stimulatory integrin and VEGF signaling in endothelial cells. Circulation Research, 101(6), 536–538.

    PubMed  CAS  Google Scholar 

  12. Mahabeleshwar, G. H., & Byzova, T. V. (2007). Angiogenesis in melanoma. Seminars in Oncology, 34(6), 555–565.

    PubMed  CAS  Google Scholar 

  13. Mahabeleshwar, G. H., Chen, J., et al. (2008). Integrin affinity modulation in angiogenesis. Cell Cycle, 7(3), 335–347.

    PubMed  CAS  Google Scholar 

  14. Mahabeleshwar, G. H., Feng, W., et al. (2006). Integrin signaling is critical for pathological angiogenesis. Journal of Experimental Medicine, 203(11), 2495–2507.

    PubMed  CAS  Google Scholar 

  15. Mahabeleshwar, G. H., Feng, W., et al. (2007). Mechanisms of integrin-vascular endothelial growth factor receptor cross-activation in angiogenesis. Circulation Research, 101(6), 570–580.

    PubMed  CAS  Google Scholar 

  16. Ogita, H., & Takai, Y. (2008). Cross-talk among integrin, cadherin, and growth factor receptor: Roles of nectin and nectin-like molecule. International Review of Cytology, 265, 1–54.

    PubMed  CAS  Google Scholar 

  17. Naik, T. U., Naik, M. U., et al. (2008). Junctional adhesion molecules in angiogenesis. Frontiers in Bioscience: A Journal and Virtual Library, 13, 258–262.

    CAS  Google Scholar 

  18. Hofer, E., & Schweighofer, B. (2007). Signal transduction induced in endothelial cells by growth factor receptors involved in angiogenesis. Thrombosis and Haemostasis, 97(3), 355–363.

    PubMed  CAS  Google Scholar 

  19. Serini, G., Napione, L., et al. (2008). Besides adhesion: New perspectives of integrin functions in angiogenesis. Cardiovascular Research, 78(2), 213–222.

    PubMed  CAS  Google Scholar 

  20. Serini, G., Napione, L., et al. (2008). Integrins team up with tyrosine kinase receptors and plexins to control angiogenesis. Current Opinion in Hematology, 15(3), 235–242.

    PubMed  CAS  Google Scholar 

  21. Suh, D. Y. (2000). Understanding angiogenesis and its clinical applications. Annals of Clinical and Laboratory Science, 30(3), 227–238.

    PubMed  CAS  Google Scholar 

  22. Muller, W. E., & Muller, I. M. (2003). Analysis of the sponge [Porifera] gene repertoire: Implications for the evolution of the metazoan body plan. Progress in Molecular and Subcellular Biology, 37, 1–33.

    PubMed  CAS  Google Scholar 

  23. Luo, B. H., Carman, C. V., et al. (2007). Structural basis of integrin regulation and signaling. Annual Review of Immunology, 25, 619–647.

    PubMed  CAS  Google Scholar 

  24. Stupack, D. G., & Cheresh, D. A. (2004). Integrins and angiogenesis. Current Topics in Developmental Biology, 64, 207–238.

    PubMed  CAS  Google Scholar 

  25. Michel, J. B. (2003). Anoikis in the cardiovascular system: Known and unknown extracellular mediators. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(12), 2146–2154.

    PubMed  CAS  Google Scholar 

  26. Bryan, B. A., & D’Amore, P. A. (2007). What tangled webs they weave: Rho-GTPase control of angiogenesis. Cellular and Molecular Life Sciences, 64(16), 2053–2065.

    PubMed  CAS  Google Scholar 

  27. Kanda, S., Miyata, Y., et al. (2007). Non-receptor protein-tyrosine kinases as molecular targets for antiangiogenic therapy (Review). International Journal of Molecular Medicine, 20(1), 113–121.

    PubMed  CAS  Google Scholar 

  28. Pouyssegur, J., Volmat, V., et al. (2002). Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling. Biochemical Pharmacology, 64(5–6), 755–763.

    PubMed  CAS  Google Scholar 

  29. Somanath, P. R., Razorenova, O. V., et al. (2006). Akt1 in endothelial cell and angiogenesis. Cell Cycle, 5(5), 512–518.

    PubMed  CAS  Google Scholar 

  30. Phillips, D. R., Nannizzi-Alaimo, L., et al. (2001). Beta3 tyrosine phosphorylation in alphaIIbbeta3 (platelet membrane GP IIb-IIIa) outside-in integrin signaling. Thrombosis and Haemostasis, 86(1), 246–258.

    PubMed  CAS  Google Scholar 

  31. Somanath, P. R., Kandel, E. S., et al. (2007). Akt1 signaling regulates integrin activation, matrix recognition, and fibronectin assembly. The Journal of Biological Chemistry, 282(31), 22964–22976.

    PubMed  CAS  Google Scholar 

  32. Borges, E., Jan, Y., et al. (2000). Platelet-derived growth factor receptor beta and vascular endothelial growth factor receptor 2 bind to the beta 3 integrin through its extracellular domain. The Journal of Biological Chemistry, 275(51), 39867–39873.

    PubMed  CAS  Google Scholar 

  33. Cybulsky, A. V., McTavish, A. J., et al. (1994). Extracellular matrix modulates epidermal growth factor receptor activation in rat glomerular epithelial cells. The Journal of Clinical Investigation, 94(1), 68–78.

    PubMed  CAS  Google Scholar 

  34. Soldi, R., Mitola, S., et al. (1999). Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. The EMBO Journal, 18(4), 882–892.

    PubMed  CAS  Google Scholar 

  35. Clemmons, D. R., Horvitz, G., et al. (1999). Synthetic alphaVbeta3 antagonists inhibit insulin-like growth factor-I-stimulated smooth muscle cell migration and replication. Endocrinology, 140(10), 4616–4621.

    PubMed  CAS  Google Scholar 

  36. Jones, P. L., Crack, J., et al. (1997). Regulation of tenascin-C, a vascular smooth muscle cell survival factor that interacts with the alpha v beta 3 integrin to promote epidermal growth factor receptor phosphorylation and growth. The Journal of Cell Biology, 139(1), 279–293.

    PubMed  CAS  Google Scholar 

  37. Maile, L. A., Badley-Clarke, J., et al. (2001). Structural analysis of the role of the beta 3 subunit of the alpha V beta 3 integrin in IGF-I signaling. Journal of Cell Science, 114(Pt 7), 1417–1425.

    PubMed  CAS  Google Scholar 

  38. Brooks, P. C., Klemke, R. L., et al. (1997). Insulin-like growth factor receptor cooperates with integrin alpha v beta 5 to promote tumor cell dissemination in vivo. The Journal of Clinical Investigation, 99(6), 1390–1398.

    PubMed  CAS  Google Scholar 

  39. Nicholson, W. C., Ge, Z., et al. (1999). Insulin-like growth factor (IGF)-I, IGF-I receptor, and IGF binding protein-3 messenger ribonucleic acids and protein in corpora lutea from prostaglandin F(2alpha)-treated gilts. Biology of Reproduction, 61(6), 1527–1534.

    PubMed  CAS  Google Scholar 

  40. Schneller, M., Vuori, K., et al. (1997). Alphavbeta3 integrin associates with activated insulin and PDGFbeta receptors and potentiates the biological activity of PDGF. The EMBO Journal, 16(18), 5600–5607.

    PubMed  CAS  Google Scholar 

  41. Serini, G., Valdembri, D., et al. (2006). Integrins and angiogenesis: A sticky business. Experimental Cell Research, 312(5), 651–658.

    PubMed  CAS  Google Scholar 

  42. Vuori, K., & Ruoslahti, E. (1994). Association of insulin receptor substrate-1 with integrins. Science, 266(5190), 1576–1578.

    PubMed  CAS  Google Scholar 

  43. Doerr, M. E., & Jones, J. I. (1996). The roles of integrins and extracellular matrix proteins in the insulin-like growth factor I-stimulated chemotaxis of human breast cancer cells. The Journal of Biological Chemistry, 271(5), 2443–2447.

    PubMed  CAS  Google Scholar 

  44. Falcioni, R., Antonini, A., et al. (1997). Alpha 6 beta 4 and alpha 6 beta 1 integrins associate with ErbB-2 in human carcinoma cell lines. Experimental Cell Research, 236(1), 76–85.

    PubMed  CAS  Google Scholar 

  45. Folgiero, V., Avetrani, P., et al. (2008). Induction of ErbB-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas. PLoS ONE, 3(2), e1592.

    PubMed  Google Scholar 

  46. Holmes, D. I., & Zachary, I. (2005). The vascular endothelial growth factor (VEGF) family: Angiogenic factors in health and disease. Genome Biology, 6(2), 209.

    PubMed  Google Scholar 

  47. Lee, C. B., & Socinski, M. A. (2007). Vascular endothelial growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer: A review of recent clinical trials. Reviews on Recent Clinical Trials, 2(2), 117–120.

    PubMed  CAS  Google Scholar 

  48. Soker, S., Takashima, S., et al. (1998). Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell, 92(6), 735–745.

    PubMed  CAS  Google Scholar 

  49. Fong, G. H., Rossant, J., et al. (1995). Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature, 376(6535), 66–70.

    PubMed  CAS  Google Scholar 

  50. Shalaby, F., Rossant, J., et al. (1995). Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature, 376(6535), 62–66.

    PubMed  CAS  Google Scholar 

  51. Nishi, J., Minamino, T., et al. (2008). Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt. Circulation Research, 103(3), 261–268.

    PubMed  CAS  Google Scholar 

  52. Sato, Y., Kanno, S., et al. (2000). Properties of two VEGF receptors, Flt-1 and KDR, in signal transduction. Annals of the New York Academy of Sciences, 902, 201–205; discussion 205–207.

    Google Scholar 

  53. Petrova, T. V., Makinen, T., et al. (1999). Signaling via vascular endothelial growth factor receptors. Experimental Cell Research, 253(1), 117–130.

    PubMed  CAS  Google Scholar 

  54. Seetharam, L., Gotoh, N., et al. (1995). A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF. Oncogene, 10(1), 135–147.

    PubMed  CAS  Google Scholar 

  55. Takahashi, T., Yamaguchi, S., et al. (2001). A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. The EMBO Journal, 20(11), 2768–2778.

    PubMed  CAS  Google Scholar 

  56. Ribatti, D. (2008). The discovery of the placental growth factor and its role in angiogenesis: A historical review. Angiogenesis, 11(3), 215–221.

    PubMed  CAS  Google Scholar 

  57. Odorisio, T., Cianfarani, F., et al. (2006). The placenta growth factor in skin angiogenesis. Journal of Dermatological Science, 41(1), 11–19.

    PubMed  CAS  Google Scholar 

  58. Xu, L., Cochran, D. M., et al. (2006). Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models. Cancer Research, 66(8), 3971–3977.

    PubMed  CAS  Google Scholar 

  59. Byzova, T. V., Goldman, C. K., et al. (2000). A mechanism for modulation of cellular responses to VEGF: Activation of the integrins. Molecular Cell, 6(4), 851–860.

    PubMed  CAS  Google Scholar 

  60. Mitola, S., Brenchio, B., et al. (2006). Type I collagen limits VEGFR-2 signaling by a SHP2 protein-tyrosine phosphatase-dependent mechanism 1. Circulation Research, 98(1), 45–54.

    PubMed  CAS  Google Scholar 

  61. De, S., Razorenova, O., et al. (2005). VEGF-integrin interplay controls tumor growth and vascularization. Proceedings of the National Academy of Sciences of the United States of America, 102(21), 7589–7594.

    PubMed  CAS  Google Scholar 

  62. Qi, J. H., & Claesson-Welsh, L. (2001). VEGF-induced activation of phosphoinositide 3-kinase is dependent on focal adhesion kinase. Experimental Cell Research, 263(1), 173–182.

    PubMed  CAS  Google Scholar 

  63. Trusolino, L., Cavassa, S., et al. (2000). HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity. The FASEB Journal, 14(11), 1629–1640.

    PubMed  CAS  Google Scholar 

  64. Inbal, A., & Dardik, R. (2006). Role of coagulation factor XIII (FXIII) in angiogenesis and tissue repair. Pathophysiology of Haemostasis and Thrombosis, 35(1–2), 162–165.

    PubMed  Google Scholar 

  65. Dardik, R., & Inbal, A. (2006). Complex formation between tissue transglutaminase II (tTG) and vascular endothelial growth factor receptor 2 (VEGFR-2): Proposed mechanism for modulation of endothelial cell response to VEGF. Experimental Cell Research, 312(16), 2973–2982.

    PubMed  CAS  Google Scholar 

  66. Wang, J. F., Zhang, X. F., et al. (2001). Stimulation of beta 1 integrin induces tyrosine phosphorylation of vascular endothelial growth factor receptor-3 and modulates cell migration. The Journal of Biological Chemistry, 276(45), 41950–41957.

    PubMed  CAS  Google Scholar 

  67. Zhang, X., Groopman, J. E., et al. (2005). Extracellular matrix regulates endothelial functions through interaction of VEGFR-3 and integrin alpha5beta1. Journal of Cellular Physiology, 202(1), 205–214.

    PubMed  CAS  Google Scholar 

  68. Yang, J. T., Rayburn, H., et al. (1993). Embryonic mesodermal defects in alpha 5 integrin-deficient mice. Development, 119(4), 1093–1105.

    PubMed  CAS  Google Scholar 

  69. Sheppard, D. (2000). In vivo functions of integrins: Lessons from null mutations in mice. Matrix Biology: Journal of the International Society for Matrix Biology, 19(3), 203–209.

    CAS  Google Scholar 

  70. Bader, B. L., Rayburn, H., et al. (1998). Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins. Cell, 95(4), 507–519.

    PubMed  CAS  Google Scholar 

  71. Reynolds, L. E., Wyder, L., et al. (2002). Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nature Medicine, 8(1), 27–34.

    PubMed  CAS  Google Scholar 

  72. Su, G., Hodnett, M., et al. (2007). Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function. American Journal of Respiratory Cell and Molecular Biology, 36(3), 377–386.

    PubMed  CAS  Google Scholar 

  73. Johnson, F. M., & Gallick, G. E. (2007). SRC family nonreceptor tyrosine kinases as molecular targets for cancer therapy. Anti-cancer Agents in Medicinal Chemistry, 7(6), 651–659.

    PubMed  CAS  Google Scholar 

  74. Kefalas, P., Brown, T. R., et al. (1995). Signalling by the p60c-src family of protein-tyrosine kinases. International Journal of Biochemistry and Cell Biology, 27(6), 551–563.

    PubMed  CAS  Google Scholar 

  75. Basson, M. D. (2008). An intracellular signal pathway that regulates cancer cell adhesion in response to extracellular forces. Cancer Research, 68(1), 2–4.

    PubMed  CAS  Google Scholar 

  76. Koppikar, P., Choi, S. H., et al. (2008). Combined inhibition of c-Src and epidermal growth factor receptor abrogates growth and invasion of head and neck squamous cell carcinoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 14(13), 4284–4291.

    CAS  Google Scholar 

  77. Coluccia, A. M., Cirulli, T., et al. (2008). Validation of PDGFRbeta and c-Src tyrosine kinases as tumor/vessel targets in patients with multiple myeloma: Preclinical efficacy of the novel, orally available inhibitor dasatinib. Blood, 112(4), 1346–1356.

    PubMed  CAS  Google Scholar 

  78. Eliceiri, B. P., Paul, R., et al. (1999). Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Molecular Cell, 4(6), 915–924.

    PubMed  CAS  Google Scholar 

  79. Schwartzberg, P. L., Xing, L., et al. (1997). Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src-/- mutant mice. Genes and Development, 11(21), 2835–2844.

    PubMed  CAS  Google Scholar 

  80. Soriano, P., Montgomery, C., et al. (1991). Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell, 64(4), 693–702.

    PubMed  CAS  Google Scholar 

  81. Lowell, C. A., & Soriano, P. (1996). Knockouts of Src-family kinases: Stiff bones, wimpy T cells, and bad memories. Genes and Development, 10(15), 1845–1857.

    PubMed  CAS  Google Scholar 

  82. Klinghoffer, R. A., Sachsenmaier, C., et al. (1999). Src family kinases are required for integrin but not PDGFR signal transduction. The EMBO Journal, 18(9), 2459–2471.

    PubMed  CAS  Google Scholar 

  83. Salmivirta, K., Talts, J. F., et al. (2002). Binding of mouse nidogen-2 to basement membrane components and cells and its expression in embryonic and adult tissues suggest complementary functions of the two nidogens. Experimental Cell Research, 279(2), 188–201.

    PubMed  CAS  Google Scholar 

  84. Klemke, R. L., Yebra, M., et al. (1994). Receptor tyrosine kinase signaling required for integrin alpha v beta 5-directed cell motility but not adhesion on vitronectin. The Journal of Cell Biology, 127(3), 859–866.

    PubMed  CAS  Google Scholar 

  85. Eliceiri, B. P., Klemke, R., et al. (1998). Integrin alphavbeta3 requirement for sustained mitogen-activated protein kinase activity during angiogenesis. The Journal of Cell Biology, 140(5), 1255–1263.

    PubMed  CAS  Google Scholar 

  86. Sahni, A., & Francis, C. W. (2004). Stimulation of endothelial cell proliferation by FGF-2 in the presence of fibrinogen requires alphavbeta3. Blood, 104(12), 3635–3641.

    PubMed  CAS  Google Scholar 

  87. Toledo, M. S., Suzuki, E., et al. (2005). Effect of ganglioside and tetraspanins in microdomains on interaction of integrins with fibroblast growth factor receptor. The Journal of Biological Chemistry, 280(16), 16227–16234.

    PubMed  CAS  Google Scholar 

  88. Yancopoulos, G. D., Davis, S., et al. (2000). Vascular-specific growth factors and blood vessel formation. Nature, 407(6801), 242–248.

    PubMed  CAS  Google Scholar 

  89. Fiedler, U., & Augustin, H. G. (2006). Angiopoietins: A link between angiogenesis and inflammation. Trends in Immunology, 27(12), 552–558.

    PubMed  CAS  Google Scholar 

  90. Minshall, R. D., & Malik, A. B. (2006). Transport across the endothelium: Regulation of endothelial permeability. Handbook of Experimental Pharmacology, 176(Pt 1), 107–144.

    PubMed  Google Scholar 

  91. Tsigkos, S., Zhou, Z., et al. (2006). Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular endothelial cells. Journal of Cellular Physiology, 207(2), 506–511.

    PubMed  CAS  Google Scholar 

  92. Roviezzo, F., Tsigkos, S., et al. (2005). Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. Journal of Pharmacology and Experimental Therapeutics, 314(2), 738–744.

    PubMed  CAS  Google Scholar 

  93. Cascone, I., Napione, L., et al. (2005). Stable interaction between alpha5beta1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1. The Journal of Cell Biology, 170(6), 993–1004.

    PubMed  CAS  Google Scholar 

  94. Thamilselvan, V., Craig, D. H., et al. (2007). FAK association with multiple signal proteins mediates pressure-induced colon cancer cell adhesion via a Src-dependent PI3 K/Akt pathway. The FASEB Journal, 21(8), 1730–1741.

    PubMed  CAS  Google Scholar 

  95. Eliceiri, B. P., Puente, X. S., et al. (2002). Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling. The Journal of Cell Biology, 157(1), 149–160.

    PubMed  CAS  Google Scholar 

  96. Lesko, E., & Majka, M. (2008). The biological role of HGF-MET axis in tumor growth and development of metastasis. Frontiers in Bioscience: A Journal and Virtual Library, 13, 1271–1280.

    CAS  Google Scholar 

  97. Comoglio, P. M., Giordano, S., et al. (2008). Drug development of MET inhibitors: Targeting oncogene addiction and expedience. Nature Reviews. Drug Discovery, 7(6), 504–516.

    PubMed  CAS  Google Scholar 

  98. Bell, L. N., Cai, L., et al. (2008). A central role for hepatocyte growth factor in adipose tissue angiogenesis. American Journal of Physiology. Endocrinology and Metabolism, 294(2), E336–E344.

    PubMed  CAS  Google Scholar 

  99. Rahman, S., Patel, Y., et al. (2005). Novel hepatocyte growth factor (HGF) binding domains on fibronectin and vitronectin coordinate a distinct and amplified Met-integrin induced signalling pathway in endothelial cells. BMC Cell Biology, 6(1), 8.

    PubMed  Google Scholar 

  100. Chung, J., Yoon, S. O., et al. (2004). The Met receptor and alpha 6 beta 4 integrin can function independently to promote carcinoma invasion. The Journal of Biological Chemistry, 279(31), 32287–32293.

    PubMed  CAS  Google Scholar 

  101. Nikolopoulos, S. N., Blaikie, P., et al. (2004). Integrin beta4 signaling promotes tumor angiogenesis. Cancer Cell, 6(5), 471–483.

    PubMed  CAS  Google Scholar 

  102. Kawasaki, T., Kitsukawa, T., et al. (1999). A requirement for neuropilin-1 in embryonic vessel formation. Development, 126(21), 4895–4902.

    PubMed  CAS  Google Scholar 

  103. Kruger, R. P., Aurandt, J., et al. (2005). Semaphorins command cells to move. Nature Reviews. Molecular Cell Biology, 6(10), 789–800.

    PubMed  CAS  Google Scholar 

  104. Soker, S., Miao, H. Q., et al. (2002). VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding. Journal of Cellular Biochemistry, 85(2), 357–368.

    PubMed  CAS  Google Scholar 

  105. Serini, G., Valdembri, D., et al. (2003). Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature, 424(6947), 391–397.

    PubMed  CAS  Google Scholar 

  106. Deutsch, U. (2004). Semaphorins guide PerPlexeD endothelial cells. Developmental Cell, 7(1), 1–2.

    PubMed  CAS  Google Scholar 

  107. Guttmann-Raviv, N., Shraga-Heled, N., et al. (2007). Semaphorin-3A and semaphorin-3F work together to repel endothelial cells and to inhibit their survival by induction of apoptosis. The Journal of Biological Chemistry, 282(36), 26294–26305.

    PubMed  CAS  Google Scholar 

  108. Geretti, E., Shimizu, A., et al. (2008). Neuropilin structure governs VEGF and semaphorin binding and regulates angiogenesis. Angiogenesis, 11(1), 31–39.

    PubMed  CAS  Google Scholar 

  109. Banu, N., Teichman, J., et al. (2006). Semaphorin 3C regulates endothelial cell function by increasing integrin activity. The FASEB Journal, 20(12), 2150–2152.

    PubMed  CAS  Google Scholar 

  110. Kinbara, K., Goldfinger, L. E., et al. (2003). Ras GTPases: Integrins’ friends or foes? Nature Reviews. Molecular Cell Biology, 4(10), 767–776.

    PubMed  CAS  Google Scholar 

  111. Oinuma, I., Ishikawa, Y., et al. (2004). The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. Science, 305(5685), 862–865.

    PubMed  CAS  Google Scholar 

  112. Dallas, S. L., Sivakumar, P., et al. (2005). Fibronectin regulates latent transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF beta-binding protein-1. The Journal of Biological Chemistry, 280(19), 18871–18880.

    PubMed  CAS  Google Scholar 

  113. Vlahakis, N. E., Young, B. A., et al. (2007). Integrin alpha9beta1 directly binds to vascular endothelial growth factor (VEGF)-A and contributes to VEGF-A-induced angiogenesis. The Journal of Biological Chemistry, 282(20), 15187–15196.

    PubMed  CAS  Google Scholar 

  114. Vlahakis, N. E., Young, B. A., et al. (2005). The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1. The Journal of Biological Chemistry, 280(6), 4544–4552.

    PubMed  CAS  Google Scholar 

  115. Kajiya, K., Hirakawa, S., et al. (2005). Hepatocyte growth factor promotes lymphatic vessel formation and function. The EMBO Journal, 24(16), 2885–2895.

    PubMed  CAS  Google Scholar 

  116. Mori, S., Wu, C. Y., et al. (2008). Direct binding of integrin alphavbeta3 to FGF1 plays a role in FGF1 signaling. The Journal of Biological Chemistry, 283(26), 18066–18075.

    PubMed  CAS  Google Scholar 

  117. Shim, W. S., Ho, I. A., et al. (2007). Angiopoietin: A TIE(d) balance in tumor angiogenesis. Molecular Cancer Research, 5(7), 655–665.

    PubMed  CAS  Google Scholar 

  118. Carlson, T. R., Feng, Y., et al. (2001). Direct cell adhesion to the angiopoietins mediated by integrins. The Journal of Biological Chemistry, 276(28), 26516–26525.

    PubMed  CAS  Google Scholar 

  119. Dallabrida, S. M., Ismail, N., et al. (2005). Angiopoietin-1 promotes cardiac and skeletal myocyte survival through integrins. Circulation Research, 96(4), e8–e24.

    PubMed  CAS  Google Scholar 

  120. Hu, B., Jarzynka, M. J., et al. (2006). Angiopoietin 2 induces glioma cell invasion by stimulating matrix metalloprotease 2 expression through the alphavbeta1 integrin and focal adhesion kinase signaling pathway. Cancer Research, 66(2), 775–783.

    PubMed  CAS  Google Scholar 

  121. Dallabrida, S. M., Ismail, N. S., et al. (2008). Integrin binding angiopoietin-1 monomers reduce cardiac hypertrophy. The FASEB Journal, 22(8), 3010–3023.

    PubMed  CAS  Google Scholar 

  122. Imanishi, Y., Hu, B., et al. (2007). Angiopoietin-2 stimulates breast cancer metastasis through the alpha(5)beta(1) integrin-mediated pathway. Cancer Research, 67(9), 4254–4263.

    PubMed  CAS  Google Scholar 

  123. Kalluri, R. (2003). Basement membranes: Structure, assembly and role in tumour angiogenesis. Nature Reviews Cancer, 3(6), 422–433.

    PubMed  CAS  Google Scholar 

  124. Shiojima, I., & Walsh, K. (2002). Role of Akt signaling in vascular homeostasis and angiogenesis. Circulation Research, 90(12), 1243–1250.

    PubMed  CAS  Google Scholar 

  125. Wickstrom, S. A., Alitalo, K., et al. (2004). An endostatin-derived peptide interacts with integrins and regulates actin cytoskeleton and migration of endothelial cells. The Journal of Biological Chemistry, 279(19), 20178–20185.

    PubMed  Google Scholar 

  126. Rehn, M., Veikkola, T., et al. (2001). Interaction of endostatin with integrins implicated in angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 98(3), 1024–1029.

    PubMed  CAS  Google Scholar 

  127. Maeshima, Y., Sudhakar, A., et al. (2002). Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science, 295(5552), 140–143.

    PubMed  CAS  Google Scholar 

  128. Sudhakar, A., Sugimoto, H., et al. (2003). Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins. Proceedings of the National Academy of Sciences of the United States of America, 100(8), 4766–4771.

    PubMed  CAS  Google Scholar 

  129. Sudhakar, A., Nyberg, P., et al. (2005). Human alpha1 type IV collagen NC1 domain exhibits distinct antiangiogenic activity mediated by alpha1beta1 integrin. The Journal of Clinical Investigation, 115(10), 2801–2810.

    PubMed  CAS  Google Scholar 

  130. Magnon, C., Galaup, A., et al. (2005). Canstatin acts on endothelial and tumor cells via mitochondrial damage initiated through interaction with alphavbeta3 and alphavbeta5 integrins. Cancer Research, 65(10), 4353–4361.

    PubMed  CAS  Google Scholar 

  131. Wahl, M. L., Kenan, D. J., et al. (2005). Angiostatin’s molecular mechanism: Aspects of specificity and regulation elucidated. Journal of Cellular Biochemistry, 96(2), 242–261.

    PubMed  CAS  Google Scholar 

  132. Gutheil, J. C., Campbell, T. N., et al. (2000). Targeted antiangiogenic therapy for cancer using Vitaxin: A humanized monoclonal antibody to the integrin alphavbeta3. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 6(8), 3056–3061.

    CAS  Google Scholar 

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Correspondence to Tatiana V. Byzova.

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Somanath, P.R., Ciocea, A. & Byzova, T.V. Integrin and Growth Factor Receptor Alliance in Angiogenesis. Cell Biochem Biophys 53, 53–64 (2009). https://doi.org/10.1007/s12013-008-9040-5

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