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

Cell Adh Migr. 2021 Dec;15(1):215-223. doi: 10.1080/19336918.2021.1951425.

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.

Keywords: Extracellular matrix; angiogenesis; collagen XIX; integrin; matrikine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Collagen / metabolism*
  • Collagen / pharmacology
  • Endothelial Cells / metabolism
  • Humans
  • Integrin alpha5beta1 / drug effects
  • Integrin alpha5beta1 / metabolism*
  • Integrin alphaVbeta3 / drug effects
  • Integrin alphaVbeta3 / metabolism*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Integrin alpha5beta1
  • Integrin alphaVbeta3
  • Peptide Fragments
  • Collagen

Grants and funding

This work was supported by the Ligue Contre le Cancer