F4, a collagen XIX-derived peptide, inhibits tumor angiogenesis through αvβ3 and α5β1 integrin interaction

F4 是一种胶原蛋白 XIX 衍生肽,通过 αvβ3 和 α5β1 整合素相互作用抑制肿瘤血管生成

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作者:Jean-Baptiste Oudart, Matthieu Villemin, Bertrand Brassart, Christèle Sellier, Christine Terryn, Aurélie Dupont-Deshorgue, Jean Claude Monboisse, François-Xavier Maquart, Laurent Ramont, Sylvie Brassart-Pasco

Abstract

We previously demonstrated that F4 peptide (CNPEDCLYPVSHAHQR) from collagen XIX was able to inhibit melanoma cell migrationin vitro and cancer progression in a mouse melanoma model. The aim of the present work was to study the anti-angiogenic properties of F4 peptide. We demonstrated that F4 peptide inhibited VEGF-induced pseudo-tube formation on Matrigel by endothelial cells and endothelial sprouting in a rat aortic ring assay. By affinity chromatography, we identified αvβ3 and α5β1 integrins as potential receptors for F4 peptide on endothelial cell surface. Using solid phase assays, we proved the direct interaction between F4 and both integrins. Taken together, our results demonstrate that F4 peptide is a potent antitumor agent inhibiting both angiogenesis and tumor cell migration.

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