Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 281, Issue 52, Pages 40450-40460Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M607525200
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- NCI NIH HHS [CA096805] Funding Source: Medline
- NHLBI NIH HHS [HL80699] Funding Source: Medline
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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(6) integrin in HBMECs. VEGF significantly increased alpha(6)beta(1) integrin expression, but not alpha(6)beta(4) integrin expression in these cells. Specific down- regulation of beta(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(6)beta(1) integrins in HBMECs. Functional blocking of alpha(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(6)beta(1) integrins, which may promote VEGF- driven tumor angiogenesis in vivo.
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