Integrin Regulation by Vascular Endothelial Growth Factor in Human Brain Microvascular Endothelial Cells ROLE OF α6β1 INTEGRIN IN ANGIOGENESIS

Abstract The precise role of vascular endothelial growth factor (VEGF) in regulating integrins in brain microvascular endothelial cells is unknown. Here, we analyzed VEGF effects on integrin expression and activation in human brain microvascular endothelial cells (HBMECs). Using human cDNA arrays and ribonuclease (RNase) protection assays, we observed that VEGF up-regulated the mRNA expression of α6 integrin in HBMECs. VEGF significantly increased α6β1 integrin expression, but not α6β4 integrin expression in these cells. Specific down-regulation of α6 integrin expression by small interfering RNA (siRNA) oligonucleotides inhibited both the capillary morphogenesis of HBMECs and their adhesion and migration. Additionally, VEGF treatment resulted in activation of α6β1 integrins in HBMECs. Functional blocking of α6 integrin with its specific antibody inhibited the VEGF-induced adhesion and migration as well as in vivo angiogenesis, and markedly suppressed tumor angiogenesis and breast carcinoma growth in vivo. Thus, VEGF can modulate angiogenesis via increased expression and activation of α6β1 integrins, which may promote VEGF-driven tumor angiogenesis in vivo.