αV integrins in angiogenesis and cancer.
During angiogenesis, αv integrins are overexpressed on the endothelial cell surface to facilitate the growth and survival of newly forming vessels. Accordingly, blocking αv integrin function by disrupting ligand binding can produce an antiangiogenic effect. Although the integrin ectodomain regulates ligand binding specificity, the short cytoplasmic tail facilitates intracellular signaling pathways through the recruitment and activation of specific kinases and signaling intermediates. This in turn controls endothelial cell adhesion, morphology, migration, invasion, proliferation, and survival. These same integrin-mediated signaling pathways are exploited in cancer to promote the invasiveness and survival of tumor cells and to manipulate the host microenvironment to provide ample blood vessel and stromal resources to support tumor growth and metastatic spread. Because expression of αv integrins on distinct cell types contributes to cancer growth, αv integrin antagonists have the potential to disrupt multiple aspects of disease progression.
Moores UCSD Cancer Center, and University of California, San Diego, La Jolla, California 92093-0803, USA; Department of Pathology, University of California, San Diego, La Jolla, California 92093-0803, USA.
Sara M
SM
Weis
David A
DA
Cheresh
D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009385:Neoplastic Processes; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D039564:Integrin alphaV