Linked Life Data

19837659

Source:http://linkedlifedata.com/resource/pubmed/id/19837659

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pubmed-article:19837659pubmed:abstractTextBoth vascular endothelial growth factor receptors (VEGFR) and integrins are major regulators of VEGF-induced angiogenesis. Previous work has shown that beta3 integrin can regulate negatively VEGFR2 expression. Here we show that beta3 integrin can regulate negatively VEGF-mediated angiogenesis by limiting the interaction of the co-receptor NRP1 (neuropilin-1) with VEGFR2. In the presence of alphav beta3 integrin, NRP1 contributed minimally to VEGF-induced angiogenic processes in vivo, ex vivo, and in vitro. Conversely, when beta3 integrin expression is absent or low or its function is blocked with RGD-mimetic inhibitors, VEGF-mediated responses became NRP1-dependent. Indeed, combined inhibition of beta3 integrin and NRP1 decreased VEGF-mediated angiogenic responses further than individual inhibition of these receptors. We also show that alphav beta3 integrin can associate with NRP1 in a VEGF-dependent fashion. Our data suggest that beta3 integrin may, in part, negatively regulate VEGF signaling by sequestering NRP1 and preventing it from interacting with VEGFR2.lld:pubmed
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pubmed-article:19837659pubmed:articleTitleAlphav beta3 integrin limits the contribution of neuropilin-1 to vascular endothelial growth factor-induced angiogenesis.lld:pubmed
pubmed-article:19837659pubmed:affiliationAdhesion and Angiogenesis Laboratory, Tumour Biology Centre, Institute of Cancer, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, United Kingdom.lld:pubmed
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