Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2006-12-25
pubmed:abstractText
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 alpha(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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40450-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17085437-Animals, pubmed-meshheading:17085437-Brain, pubmed-meshheading:17085437-Cell Line, pubmed-meshheading:17085437-Cell Line, Tumor, pubmed-meshheading:17085437-Endothelium, Vascular, pubmed-meshheading:17085437-Female, pubmed-meshheading:17085437-Humans, pubmed-meshheading:17085437-Integrin alpha6beta1, pubmed-meshheading:17085437-Mice, pubmed-meshheading:17085437-Mice, Nude, pubmed-meshheading:17085437-Microcirculation, pubmed-meshheading:17085437-Neovascularization, Pathologic, pubmed-meshheading:17085437-Neovascularization, Physiologic, pubmed-meshheading:17085437-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17085437-RNA, Messenger, pubmed-meshheading:17085437-Receptors, Vascular Endothelial Growth Factor, pubmed-meshheading:17085437-Vascular Endothelial Growth Factor A
pubmed:year
2006
pubmed:articleTitle
Integrin regulation by vascular endothelial growth factor in human brain microvascular endothelial cells: role of alpha6beta1 integrin in angiogenesis.
pubmed:affiliation
Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural