Inhibition of endothelial cell migration and angiogenesis by a vascular endothelial growth factor receptor-1 derived peptide

Pedro M. Lacal, Veronica Morea, Federica Ruffini, Angela Orecchia, Annalisa S. Dorio, Cristina M. Failla, Simonetta Soro, Lucio Tentori, Giovanna Zambruno, Grazia Graziani, Anna Tramontano, Stefania D'Atri

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Abstract

Vascular endothelial growth factor receptor-1 (VEGFR-1) exists in two isoforms: a membrane-bound isoform (mVEGFR-1) and a soluble one (sVEGFR-1). mVEGFR-1 is involved in endothelial cell migration and survival supported by VEGF-A and placenta growth factor (PlGF), whereas the biologic function of sVEGFR-1 has not been fully elucidated. We previously reported that sVEGFR-1 induces endothelial cell motility and promotes endothelial cell adhesion. In this study, we tested a set of VEGFR-1-derived peptides for their ability to interfere with endothelial cell migration. Peptide B3 was found to specifically inhibit cell migration induced by sVEGFR-1 and by mVEGFR-1-specific ligands. Moreover, peptide B3 markedly hampered angiogenesis in vitro and in vivo and was found to interfere with VEGFR-1 homodimerisation. Altogether, these data demonstrate that peptide B3 might be a useful tool for the specific inhibition of VEGFR-1 function and might represent a basis for the development of new anti-angiogenic compounds.

Original languageEnglish
Pages (from-to)1914-1921
Number of pages8
JournalEuropean Journal of Cancer
Volume44
Issue number13
DOIs
Publication statusPublished - Sep 2008

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Keywords

  • Angiogenesis
  • Endothelial cells
  • Migration
  • PlGF
  • Soluble VEGFR-1
  • VEGFR-1 activation
  • VEGFR-1 peptides

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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