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Integrins in Angiogenesis

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Angiogenesis

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Angiogenesis, the formation of new blood vessels from pre-existing vessels, plays a prominent role in a variety of pathological conditions, including tumor growth, ocular disease and arthritis. Endothelial cell adhesion to the extracellular matrix (ECM) permits transduction of signals initiated by angiogenic growth factors leading to activation of distinct signaling pathways that promote endothelial cell proliferation, migration/invasion and survival. Integrins play a pivotal role in promoting the transfer of chemical and mechanical signals from the extracellular environment into the intracellular compartment. Here, we review recent advances in our understanding of the role of distinct integrins in mediating endothelial cell invasion, migration, and importantly, their role in regulating the survival of invasive cells as they encounter distinct new microenvironments. Progress in the use of integrin antagonists as antiangiogenic agents in the clinic will be summarized.

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References

  1. Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell 1996;87(7):1153–5.

    PubMed  CAS  Google Scholar 

  2. Ingber DE, Folkman J. Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. The Journal of cell biology 1989;109(1):317–30.

    PubMed  CAS  Google Scholar 

  3. Kalebic T, Garbisa S, Glaser B, Liotta LA. Basement membrane collagen: degradation by migrating endothelial cells. Science 1983;221(4607):281–3.

    PubMed  CAS  Google Scholar 

  4. Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992;69(1):11–25.

    PubMed  CAS  Google Scholar 

  5. Sastry SK, Burridge K. Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Experimental cell research 2000;261(1):25–36.

    PubMed  CAS  Google Scholar 

  6. DeMali KA, Wennerberg K, Burridge K. Integrin signaling to the actin cytoskeleton. Current opinion in cell biology 2003;15(5): 572–82.

    PubMed  CAS  Google Scholar 

  7. Boudreau N, Andrews C, Srebrow A, Ravanpay A, Cheresh DA. Induction of the angiogenic phenotype by Hox D3. The Journal of cell biology 1997;139(1):257–64.

    PubMed  CAS  Google Scholar 

  8. Lyden D, Young AZ, Zagzag D, et al. Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 1999;401(6754):670–7.

    PubMed  CAS  Google Scholar 

  9. Ginsberg MH, Du X, Plow EF. Inside-out integrin signalling. Current opinion in cell biology 1992;4(5):766–71.

    PubMed  CAS  Google Scholar 

  10. Senger DR, Claffey KP, Benes JE, Perruzzi CA, Sergiou AP, Detmar M. Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins. Proceedings of the National Academy of Sciences of the United States of America 1997;94(25): 13612–7.

    PubMed  CAS  Google Scholar 

  11. Kim S, Bell K, Mousa SA, Varner JA. Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin. The American journal of pathology 2000;156(4):1345–62.

    PubMed  CAS  Google Scholar 

  12. Okada Y, Copeland BR, Hamann GF, Koziol JA, Cheresh DA, del Zoppo GJ. Integrin alphavbeta3 is expressed in selected microvessels after focal cerebral ischemia. The American journal of pathology 1996;149(1):37–44.

    PubMed  CAS  Google Scholar 

  13. Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 1994;264(5158): 569–71.

    PubMed  CAS  Google Scholar 

  14. Garmy-Susini B, Jin H, Zhu Y, Sung RJ, Hwang R, Varner J. Integrin alpha4beta1-VCAM-1-mediated adhesion between endothelial and mural cells is required for blood vessel maturation. The Journal of clinical investigation 2005;115(6): 1542–51.

    PubMed  CAS  Google Scholar 

  15. Hiran TS, Mazurkiewicz JE, Kreienberg P, Rice FL, LaFlamme SE. Endothelial expression of the alpha6beta4 integrin is negatively regulated during angiogenesis. Journal of cell science 2003;116(Pt 18):3771–81.

    PubMed  CAS  Google Scholar 

  16. Yokosaki Y, Palmer EL, Prieto AL, et al. The integrin alpha 9 beta 1 mediates cell attachment to a non-RGD site in the third fibronectin type III repeat of tenascin. The Journal of biological chemistry 1994;269(43):26691–6.

    PubMed  CAS  Google Scholar 

  17. Smith LL, Cheung HK, Ling LE, et al. Osteopontin N-terminal domain contains a cryptic adhesive sequence recognized by alpha9beta1 integrin. The Journal of biological chemistry 1996;271(45):28485–91.

    PubMed  CAS  Google Scholar 

  18. Taooka Y, Chen J, Yednock T, Sheppard D. The integrin alpha9beta1 mediates adhesion to activated endothelial cells and transendothelial neutrophil migration through interaction with vascular cell adhesion molecule-1. The Journal of cell biology 1999;145(2):413–20.

    PubMed  CAS  Google Scholar 

  19. Huang XZ, Wu JF, Ferrando R, et al. Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1. Molecular and cellular biology 2000;20(14):5208–15.

    PubMed  CAS  Google Scholar 

  20. Francis SE, Goh KL, Hodivala-Dilke K, et al. Central roles of alpha5beta1 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies. Arteriosclerosis, thrombosis, and vascular biology 2002;22(6):927–33.

    PubMed  CAS  Google Scholar 

  21. Yang JT, Rayburn H, Hynes RO. Embryonic mesodermal defects in alpha 5 integrin-deficient mice. Development (Cambridge, England) 1993;119(4):1093–105.

    CAS  Google Scholar 

  22. Bader BL, Rayburn H, Crowley D, Hynes RO. Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins. Cell 1998;95(4):507–19.

    PubMed  CAS  Google Scholar 

  23. Zhu J, Motejlek K, Wang D, Zang K, Schmidt A, Reichardt LF. beta8 integrins are required for vascular morphogenesis in mouse embryos. Development (Cambridge, England) 2002;129(12):2891–903.

    CAS  Google Scholar 

  24. Hodivala-Dilke KM, McHugh KP, Tsakiris DA, et al. Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. The Journal of clinical investigation 1999;103(2):229–38.

    PubMed  CAS  Google Scholar 

  25. Huang X, Griffiths M, Wu J, Farese RV, Jr., Sheppard D. Normal development, wound healing, and adenovirus susceptibility in beta5-deficient mice. Molecular and cellular biology 2000;20(3):755–9.

    PubMed  CAS  Google Scholar 

  26. Huang XZ, Wu JF, Cass D, et al. Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin. The Journal of cell biology 1996;133(4):921–8.

    PubMed  CAS  Google Scholar 

  27. Reynolds LE, Wyder L, Lively JC, et al. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nature medicine 2002;8(1):27–34.

    PubMed  CAS  Google Scholar 

  28. Reynolds LE, Conti FJ, Lucas M, et al. Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling. Nature medicine 2005;11(2): 167–74.

    PubMed  CAS  Google Scholar 

  29. Taverna D, Moher H, Crowley D, Borsig L, Varki A, Hynes RO. Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins or selectins. Proceedings of the National Academy of Sciences of the United States of America 2004;101(3):763–8.

    PubMed  CAS  Google Scholar 

  30. Weis SM, Lindquist JN, Barnes LA, et al. Cooperation between VEGF and {beta}3 integrin during cardiac vascular development. Blood 2006.

    Google Scholar 

  31. Schneller M, Vuori K, Ruoslahti E. Alphavbeta3 integrin associates with activated insulin and PDGFbeta receptors and potentiates the biological activity of PDGF. The EMBO journal 1997;16(18):5600–7.

    PubMed  CAS  Google Scholar 

  32. Borges E, Jan Y, Ruoslahti E. 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 2000;275(51):39867–73.

    PubMed  CAS  Google Scholar 

  33. Bergers G, Brekken R, McMahon G, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nature cell biology 2000;2(10):737–44.

    PubMed  CAS  Google Scholar 

  34. Brooks PC, Stromblad S, Sanders LC, et al. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 1996;85(5): 683–93.

    PubMed  CAS  Google Scholar 

  35. Brooks PC, Silletti S, von Schalscha TL, Friedlander M, Cheresh DA. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 1998;92(3):391–400.

    PubMed  CAS  Google Scholar 

  36. Xu J, Rodriguez D, Petitclerc E, et al. Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. The Journal of cell biology 2001;154(5):1069–79.

    PubMed  CAS  Google Scholar 

  37. Clark RA, Tonnesen MG, Gailit J, Cheresh DA. Transient functional expression of alphaVbeta 3 on vascular cells during wound repair. The American journal of pathology 1996;148(5): 1407–21.

    PubMed  CAS  Google Scholar 

  38. Nagy JA, Brown LF, Senger DR, et al. Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. Biochimica et biophysica acta 1989;948(3): 305–26.

    PubMed  CAS  Google Scholar 

  39. Dvorak HF, Harvey VS, Estrella P, Brown LF, McDonagh J, Dvorak AM. Fibrin containing gels induce angiogenesis. Implications for tumor stroma generation and wound healing. Laboratory investigation; a journal of technical methods and pathology 1987;57(6):673–86.

    PubMed  CAS  Google Scholar 

  40. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. The New England journal of medicine 1986;315(26):1650–9.

    Article  PubMed  CAS  Google Scholar 

  41. Bayless KJ, Salazar R, Davis GE. RGD-dependent vacuolation and lumen formation observed during endothelial cell morphogenesis in three-dimensional fibrin matrices involves the alpha(v) beta(3) and alpha(5) beta(1) integrins. The American journal of pathology 2000;156(5):1673–83.

    PubMed  CAS  Google Scholar 

  42. van Hinsbergh VW, Collen A, Koolwijk P. Role of fibrin matrix in angiogenesis. Annals of the New York Academy of Sciences 2001;936:426–37.

    PubMed  Google Scholar 

  43. Montgomery AMP, Reisfeld RA, Cheresh DA. Integrin {alpha}v{beta}3 Rescues Melanoma Cells from Apoptosis in Three-Dimensional Dermal Collagen. In; 1994:8856–60.

    Google Scholar 

  44. Senger DR, Perruzzi CA, Streit M, Koteliansky VE, de Fougerolles AR, Detmar M. The alpha(1) beta(1) and alpha(2) beta(1) integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. The American journal of pathology 2002;160(1): 195–204.

    PubMed  CAS  Google Scholar 

  45. Eliceiri BP, Klemke R, Stromblad S, Cheresh DA. Integrin alphavbeta3 requirement for sustained mitogen-activated protein kinase activity during angiogenesis. The Journal of cell biology 1998;140(5):1255–63.

    PubMed  CAS  Google Scholar 

  46. Stupack DG, Puente XS, Boutsaboualoy S, Storgard CM, Cheresh DA. Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins. The Journal of cell biology 2001;155(3):459–70.

    PubMed  CAS  Google Scholar 

  47. Scatena M, Almeida M, Chaisson ML, Fausto N, Nicosia RF, Giachelli CM. NF-kappaB mediates alphavbeta3 integrin-induced endothelial cell survival. The Journal of cell biology 1998;141(4):1083–93.

    PubMed  CAS  Google Scholar 

  48. Stromblad S, Becker JC, Yebra M, Brooks PC, Cheresh DA. Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin alphaVbeta3 during angiogenesis. The Journal of clinical investigation 1996;98(2):426–33.

    PubMed  CAS  Google Scholar 

  49. Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA, Cheresh DA. Definition of two angiogenic pathways by distinct alpha v integrins. Science 1995;270(5241):1500–2.

    PubMed  CAS  Google Scholar 

  50. Hammes HP, Brownlee M, Jonczyk A, Sutter A, Preissner KT. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization. Nature medicine 1996;2(5):529–33.

    PubMed  CAS  Google Scholar 

  51. Maeshima Y, Yerramalla UL, Dhanabal M, et al. Extracellular matrix-derived peptide binds to alpha(v) beta(3) integrin and inhibits angiogenesis. The Journal of biological chemistry 2001;276(34):31959–68.

    PubMed  CAS  Google Scholar 

  52. Stupack DG, Cheresh DA. Get a ligand, get a life: integrins, signaling and cell survival. Journal of cell science 2002;115(Pt 19):3729–38.

    PubMed  CAS  Google Scholar 

  53. Mehlen P, Puisieux A. Metastasis: a question of life or death. Nature reviews 2006;6(6):449–58.

    PubMed  CAS  Google Scholar 

  54. Stupack DG, Teitz T, Potter MD, et al. Potentiation of neuroblastoma metastasis by loss of caspase-8. Nature 2006;439(7072): 95–9.

    PubMed  CAS  Google Scholar 

  55. Maeshima Y, Colorado PC, Kalluri R. Two RGD-independent alpha vbeta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties. The Journal of biological chemistry 2000;275(31):23745–50.

    PubMed  CAS  Google Scholar 

  56. Giancotti FG, Ruoslahti E. Integrin signaling. Science 1999;285(5430):1028–32.

    PubMed  CAS  Google Scholar 

  57. Storgard CM, Stupack DG, Jonczyk A, Goodman SL, Fox RI, Cheresh DA. Decreased angiogenesis and arthritic disease in rabbits treated with an alphavbeta3 antagonist. The Journal of clinical investigation 1999;103(1):47–54.

    PubMed  CAS  Google Scholar 

  58. Jan Y, Matter M, Pai JT, et al. A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors. Cell 2004;116(5):751–62.

    PubMed  CAS  Google Scholar 

  59. Dhanabal M, Ramchandran R, Waterman MJ, et al. Endostatin induces endothelial cell apoptosis. The Journal of biological chemistry 1999;274(17):11721–6.

    PubMed  CAS  Google Scholar 

  60. Frisch SM, Screaton RA. Anoikis mechanisms. Current opinion in cell biology 2001;13(5):555–62.

    PubMed  CAS  Google Scholar 

  61. Brooks PC, Stromblad S, Klemke R, Visscher D, Sarkar FH, Cheresh DA. Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. The Journal of clinical investigation 1995;96(4):1815–22.

    PubMed  CAS  Google Scholar 

  62. Friedlander M, Theesfeld CL, Sugita M, et al. Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. Proceedings of the National Academy of Sciences of the United States of America 1996;93(18):9764–9.

    PubMed  CAS  Google Scholar 

  63. Stromblad S, Fotedar A, Brickner H, et al. Loss of p53 compensates for alpha v-integrin function in retinal neovascularization. The Journal of biological chemistry 2002;277(16): 13371–4.

    PubMed  CAS  Google Scholar 

  64. Hamano Y, Zeisberg M, Sugimoto H, et al. Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer cell 2003;3(6):589–601.

    PubMed  CAS  Google Scholar 

  65. Maeshima Y, Manfredi M, Reimer C, et al. Identification of the anti-angiogenic site within vascular basement membrane- derived tumstatin. The Journal of biological chemistry 2001;276(18):15240–8.

    PubMed  CAS  Google Scholar 

  66. Sudhakar A, Sugimoto H, Yang C, Lively J, Zeisberg M, Kalluri R. 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 2003;100(8):4766–71.

    PubMed  CAS  Google Scholar 

  67. Maeshima Y, Sudhakar A, Lively JC, et al. Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science 2002;295(5552):140–3.

    PubMed  CAS  Google Scholar 

  68. Stupack DG. Integrins as a distinct subtype of dependence receptors. Cell death and differentiation 2005;12(8):1021–30.

    PubMed  CAS  Google Scholar 

  69. Eliceiri BP, Paul R, Schwartzberg PL, Hood JD, Leng J, Cheresh DA. Selective Requirement for Src Kinases during VEGF-Induced Angiogenesis and Vascular Permeability. Molecular Cell 1999;4(6):915–24.

    PubMed  CAS  Google Scholar 

  70. Alavi A, Hood JD, Frausto R, Stupack DG, Cheresh DA. Role of Raf in vascular protection from distinct apoptotic stimuli. Science 2003;301(5629):94–6.

    PubMed  CAS  Google Scholar 

  71. Hood JD, Bednarski M, Frausto R, et al. Tumor regression by targeted gene delivery to the neovasculature. Science 2002;296(5577): 2404–7.

    PubMed  CAS  Google Scholar 

  72. Kalluri R. Basement membranes: structure, assembly and role in tumour angiogenesis. Nature reviews 2003;3(6):422–33.

    PubMed  CAS  Google Scholar 

  73. Colorado PC, Torre A, Kamphaus G, et al. Anti-angiogenic cues from vascular basement membrane collagen. Cancer research 2000;60(9):2520–6.

    PubMed  CAS  Google Scholar 

  74. Kim YM, Jang JW, Lee OH, et al. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase. Cancer research 2000;60(19):5410–3.

    PubMed  CAS  Google Scholar 

  75. O’Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997;88(2):277–85.

    PubMed  Google Scholar 

  76. O’Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994;79(2):315–28.

    PubMed  Google Scholar 

  77. Kamphaus GD, Colorado PC, Panka DJ, et al. Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. The Journal of biological chemistry 2000;275(2):1209–15.

    PubMed  CAS  Google Scholar 

  78. Petitclerc E, Boutaud A, Prestayko A, et al. New functions for non-collagenous domains of human collagen type IV. Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo. The Journal of biological chemistry 2000;275(11): 8051–61.

    PubMed  CAS  Google Scholar 

  79. Nyberg P, Xie L, Kalluri R. Endogenous inhibitors of angiogenesis. Cancer research 2005;65(10):3967–79.

    PubMed  CAS  Google Scholar 

  80. Kim YM, Hwang S, Kim YM, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1. The Journal of biological chemistry 2002;277(31):27872–9.

    PubMed  CAS  Google Scholar 

  81. Rehn M, Veikkola T, Kukk-Valdre E, et al. Interaction of endostatin with integrins implicated in angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 2001;98(3):1024–9.

    PubMed  CAS  Google Scholar 

  82. Ferreras M, Felbor U, Lenhard T, Olsen BR, Delaisse J. Generation and degradation of human endostatin proteins by various proteinases. FEBS letters 2000;486(3):247–51.

    PubMed  CAS  Google Scholar 

  83. Maeshima Y, Colorado PC, Torre A, et al. Distinct antitumor properties of a type IV collagen domain derived from basement membrane. The Journal of biological chemistry 2000;275(28):21340–8.

    PubMed  CAS  Google Scholar 

  84. Hynes RO. A reevaluation of integrins as regulators of angiogenesis. Nature medicine 2002;8(9):918–21.

    PubMed  CAS  Google Scholar 

  85. Dhanabal M, Volk R, Ramchandran R, Simons M, Sukhatme VP. Cloning, expression, and in vitro activity of human endostatin. Biochemical and biophysical research communications 1999;258(2):345–52.

    PubMed  CAS  Google Scholar 

  86. Yamaguchi N, Anand-Apte B, Lee M, et al. Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding. The EMBO journal 1999;18(16): 4414–23.

    PubMed  CAS  Google Scholar 

  87. Sund M, Hamano Y, Sugimoto H, et al. Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors. Proceedings of the National Academy of Sciences of the United States of America 2005;102(8):2934–9.

    PubMed  CAS  Google Scholar 

  88. Lee SJ, Jang JW, Kim YM, et al. Endostatin binds to the catalytic domain of matrix metalloproteinase-2. FEBS letters 2002;519 (1–3):147–52.

    PubMed  CAS  Google Scholar 

  89. Nyberg P, Heikkila P, Sorsa T, et al. Endostatin inhibits human tongue carcinoma cell invasion and intravasation and blocks the activation of matrix metalloprotease-2, -9, and -13. The Journal of biological chemistry 2003;278(25):22404–11.

    PubMed  CAS  Google Scholar 

  90. Pfeifer A, Kessler T, Silletti S, Cheresh DA, Verma IM. Suppression of angiogenesis by lentiviral delivery of PEX, a noncatalytic fragment of matrix metalloproteinase 2. Proceedings of the National Academy of Sciences of the United States of America 2000;97(22):12227–32.

    PubMed  CAS  Google Scholar 

  91. Deryugina EI, Bourdon MA, Jungwirth K, Smith JW, Strongin AY. Functional activation of integrin alpha V beta 3 in tumor cells expressing membrane-type 1 matrix metalloproteinase. International journal of cancer 2000;86(1):15–23.

    CAS  Google Scholar 

  92. Gerhardt H, Betsholtz C. Endothelial-pericyte interactions in angiogenesis. Cell and tissue research 2003;314(1):15–23.

    PubMed  Google Scholar 

  93. Jain RK, Booth MF. What brings pericytes to tumor vessels? The Journal of clinical investigation 2003;112(8):1134–6.

    PubMed  CAS  Google Scholar 

  94. Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development (Cambridge, England) 1999;126(14):3047–55.

    CAS  Google Scholar 

  95. Hellstrom M, Gerhardt H, Kalen M, et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. The Journal of cell biology 2001;153(3):543–53.

    PubMed  CAS  Google Scholar 

  96. Mecham RP, Stenmark KR, Parks WC. Connective tissue production by vascular smooth muscle in development and disease. Chest 1991;99(3 Suppl):43S–7S.

    PubMed  CAS  Google Scholar 

  97. Tan EM, Glassberg E, Olsen DR, et al. Extracellular matrix gene expression by human endothelial and smooth muscle cells. Matrix (Stuttgart, Germany) 1991;11(6):380–7.

    CAS  Google Scholar 

  98. Grazioli A, Alves CS, Konstantopoulos K, Yang JT. Defective blood vessel development and pericyte/pvSMC distribution in alpha 4 integrin-deficient mouse embryos. Developmental biology 2006;293(1):165–77.

    PubMed  CAS  Google Scholar 

  99. Goldfinger LE, Han J, Kiosses WB, Howe AK, Ginsberg MH. Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4beta1-dependent cell migration. The Journal of cell biology 2003;162(4):731–41.

    PubMed  CAS  Google Scholar 

  100. Sengbusch JK, He W, Pinco KA, Yang JT. Dual functions of [alpha]4[beta]1 integrin in epicardial development: initial migration and long-term attachment. The Journal of cell biology 2002;157(5):873–82.

    PubMed  CAS  Google Scholar 

  101. Kassner PD, Hemler ME. Interchangeable alpha chain cytoplasmic domains play a positive role in control of cell adhesion mediated by VLA-4, a beta 1 integrin. The Journal of experimental medicine 1993;178(2):649–60.

    PubMed  CAS  Google Scholar 

  102. Pinco KA, He W, Yang JT. alpha4beta1 integrin regulates lamellipodia protrusion via a focal complex/focal adhesion- independent mechanism. Molecular biology of the cell 2002;13(9):3203–17.

    PubMed  CAS  Google Scholar 

  103. Nishiya N, Kiosses WB, Han J, Ginsberg MH. An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells. Nature cell biology 2005;7(4):343–52.

    PubMed  CAS  Google Scholar 

  104. Sheppard AM, Onken MD, Rosen GD, Noakes PG, Dean DC. Expanding roles for alpha 4 integrin and its ligands in development. Cell adhesion and communication 1994;2(1):27–43.

    PubMed  CAS  Google Scholar 

  105. Osborn L, Hession C, Tizard R, et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 1989;59(6):1203–11.

    PubMed  CAS  Google Scholar 

  106. Elices MJ, Osborn L, Takada Y, et al. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 1990;60(4):577–84.

    PubMed  CAS  Google Scholar 

  107. Guan JL, Hynes RO. Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1. Cell 1990;60(1):53–61.

    PubMed  CAS  Google Scholar 

  108. Jain RK, Duda DG. Role of bone marrow-derived cells in tumor angiogenesis and treatment. Cancer cell 2003;3(6):515–6.

    PubMed  CAS  Google Scholar 

  109. Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. The Journal of clinical investigation 2004;114(3):330–8.

    PubMed  CAS  Google Scholar 

  110. Cursiefen C, Chen L, Borges LP, et al. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. The Journal of clinical investigation 2004;113(7):1040–50.

    PubMed  CAS  Google Scholar 

  111. Scapini P, Morini M, Tecchio C, 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.

    PubMed  CAS  Google Scholar 

  112. Jin H, Su J, Garmy-Susini B, Kleeman J, Varner J. Integrin alpha4beta1 promotes monocyte trafficking and angiogenesis in tumors. Cancer research 2006;66(4):2146–52.

    PubMed  CAS  Google Scholar 

  113. Jin H, Aiyer A, Su J, et al. A homing mechanism for bone marrow-derived progenitor cell recruitment to the neovasculature. The Journal of clinical investigation 2006;116(3):652–62.

    PubMed  CAS  Google Scholar 

  114. Ruzinova MB, Schoer RA, Gerald W, et al. Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer cell 2003;4(4):277–89.

    PubMed  CAS  Google Scholar 

  115. Dietrich J, Lacagnina M, Gass D, et al. EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy. Nature medicine 2005;11(3):277–83.

    PubMed  CAS  Google Scholar 

  116. Haubner R, Schmitt W, Holzemann G, Goodman SL, Jonczyk A, Kessler H. Cyclic RGD Peptides Containing β-Turn Mimetics. In; 1996:7881–91.

    Google Scholar 

  117. Mitjans F, Meyer T, Fittschen C, et al. In vivo therapy of malignant melanoma by means of antagonists of alphav integrins. International journal of cancer 2000;87(5):716–23.

    CAS  Google Scholar 

  118. Miller WH, Keenan RM, Willette RN, Lark MW. Identification and in vivo efficacy of small-molecule antagonists of integrin alphavbeta3 (the vitronectin receptor). Drug Discov Today 2000;5(9):397–408.

    PubMed  CAS  Google Scholar 

  119. Goodman SL, Holzemann G, Sulyok GA, Kessler H. Nanomolar small molecule inhibitors for alphav(beta) 6, alphav(beta) 5, and alphav(beta) 3 integrins. Journal of medicinal chemistry 2002;45(5):1045–51.

    PubMed  CAS  Google Scholar 

  120. Gutheil JC, Campbell TN, Pierce PR, et al. Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res 2000;6(8):3056–61.

    PubMed  CAS  Google Scholar 

  121. McNeel DG, Eickhoff J, Lee FT, 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.

    PubMed  CAS  Google Scholar 

  122. Ramakrishnan V, Bhaskar V, Law DA, et al. Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti-angiogenic agent. Journal of experimental therapeutics & oncology 2006;5(4):273–86.

    CAS  Google Scholar 

  123. Trikha M, Zhou Z, Nemeth JA, et al. CNTO 95, a fully human monoclonal antibody that inhibits alphav integrins, has antitumor and antiangiogenic activity in vivo. International journal of cancer 2004;110(3):326–35.

    CAS  Google Scholar 

  124. Jayson GC, Mullamitha S, Ton C, et al. Phase I study of CNTO 95, a fully human monoclonal antibody (mAb) to {alpha}v integrins, in patients with solid tumors. In; 2005:3113-.

    Google Scholar 

  125. Smith JW. Cilengitide Merck. Curr Opin Investig Drugs 2003;4(6):741–5.

    PubMed  CAS  Google Scholar 

  126. Eskens FA, Dumez H, Hoekstra R, et al. Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours. Eur J Cancer 2003;39(7):917–26.

    PubMed  CAS  Google Scholar 

  127. Carron CP, Meyer DM, Pegg JA, et al. A peptidomimetic antagonist of the integrin alpha(v) beta3 inhibits Leydig cell tumor growth and the development of hypercalcemia of malignancy. Cancer research 1998;58(9):1930–5.

    PubMed  CAS  Google Scholar 

  128. Reinmuth N, Liu W, Ahmad SA, et al. Alphavbeta3 integrin antagonist S247 decreases colon cancer metastasis and angiogenesis and improves survival in mice. Cancer research 2003;63(9):2079–87.

    PubMed  CAS  Google Scholar 

  129. Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KC. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nature medicine 1998;4(5):623–6.

    PubMed  CAS  Google Scholar 

  130. Winter PM, Morawski AM, Caruthers SD, et al. Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With {alpha}v{beta}3-Integrin-Targeted Nanoparticles. In; 2003:2270–4.

    Google Scholar 

  131. Chen X, Park R, Shahinian AH, et al. 18F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis. Nuclear medicine and biology 2004;31(2):179–89.

    PubMed  CAS  Google Scholar 

  132. Chen X, Park R, Tohme M, Shahinian AH, Bading JR, Conti PS. MicroPET and autoradiographic imaging of breast cancer alpha v-integrin expression using 18F- and 64Cu-labeled RGD peptide. Bioconjugate chemistry 2004;15(1):41–9.

    PubMed  Google Scholar 

  133. Haubner R, Kuhnast B, Mang C, et al. [18F]Galacto-RGD: synthesis, radiolabeling, metabolic stability, and radiation dose estimates. Bioconjugate chemistry 2004;15(1):61–9.

    PubMed  CAS  Google Scholar 

  134. Haubner R, Wester HJ, Weber WA, et al. Noninvasive imaging of alpha(v) beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer research 2001;61(5):1781–5.

    PubMed  CAS  Google Scholar 

  135. Cai W, Wu Y, Chen K, Cao Q, Tice DA, Chen X. In vitro and In vivo Characterization of 64Cu-Labeled AbegrinTM, a Humanized Monoclonal Antibody against Integrin {alpha}v{beta}3. Cancer research 2006;66(19):9673–81.

    PubMed  CAS  Google Scholar 

  136. Janssen M, Oyen WJ, Massuger LF, et al. Comparison of a monomeric and dimeric radiolabeled RGD-peptide for tumor targeting. Cancer biotherapy & radiopharmaceuticals 2002;17(6):641–6.

    CAS  Google Scholar 

  137. Janssen ML, Oyen WJ, Dijkgraaf I, et al. Tumor targeting with radiolabeled alpha(v) beta(3) integrin binding peptides in a nude mouse model. Cancer research 2002;62(21):6146–51.

    PubMed  CAS  Google Scholar 

  138. Chen X, Conti PS, Moats RA. In vivo near-infrared fluorescence imaging of integrin alphavbeta3 in brain tumor xenografts. Cancer research 2004;64(21):8009–14.

    PubMed  CAS  Google Scholar 

  139. Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 1998;279(5349):377–80.

    PubMed  CAS  Google Scholar 

  140. Schiffelers RM, Koning GA, ten Hagen TL, et al. Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. J Control Release 2003;91(1–2):115–22.

    PubMed  CAS  Google Scholar 

  141. Kasono K, Blackwell JL, Douglas JT, et al. Selective gene delivery to head and neck cancer cells via an integrin targeted adenoviral vector. Clin Cancer Res 1999;5(9):2571–9.

    PubMed  CAS  Google Scholar 

  142. Schiffelers RM, Ansari A, Xu J, et al. Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic acids research 2004;32(19):e149.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Moores Cancer Center, University of California, San Diego, CA, USA

    Alireza S. Alavi & David A. Cheresh

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  1. Alireza S. Alavi
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  1. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    William D. Figg

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

    Judah Folkman

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Alavi, A.S., Cheresh, D.A. (2008). Integrins in Angiogenesis. In: Figg, W.D., Folkman, J. (eds) Angiogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71518-6_6

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