Integrin Regulation by Vascular Endothelial Growth Factor in Human Brain Microvascular Endothelial Cells: ROLE OF alpha sub(6) beta sub(1) INTEGRIN IN ANGIOGENESIS

• Published in: The Journal of biological chemistry Vol. 281; no. 52; pp. 40450 - 40460
• Main Authors: Lee, Tae-Hee, Seng, Seyha, Li, Huchun, Kennel, Stephen J, Avraham, Hava Karsenty, Avraham, Shalom
• Format: Journal Article
• Language: English
• Published: 01-12-2006
• ISSN: 0021-9258; 1083-351X

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 alpha sub(6) integrin in HBMECs. VEGF significantly increased alpha sub(6) beta sub(1) integrin expression, but not alpha sub(6) beta sub(4) integrin expression in these cells. Specific down-regulation of alpha sub(6) 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 alpha sub(6) beta sub(1) integrins in HBMECs. Functional blocking of alpha sub(6) 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 alpha sub(6) beta sub(1) integrins, which may promote VEGF-driven tumor angiogenesis in vivo.