Abstract

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.

Highlights

  • IntroductionTumors develop a neovascular network [2]

  • During tumor growth, more nutrient and oxygen are required [1]

  • We showed that plasmin, one predominant enzyme involved in tumor

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Summary

Introduction

Tumors develop a neovascular network [2] This vascular network favors tumor cell proliferation, invasion and metastatic disse­ mination [3]. This process, commonly named ‘angio­ genic switch’, corresponds to an imbalance between pro- and anti-angiogenic molecules [4,5]. Pro-angiogenic factor as vascular growth factors (VEGFs), fibroblast growth factors (FGFs), platelet-derived growth factors (PDGFs) promote tumor angiogenesis [12,13]. Their numerous signaling pathways are interconnected with those triggered by integrins [14]

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