Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for the α5β1 integrin

Angela Orecchia, Pedro Miguel Lacal, Cataldo Schietroma, Veronica Morea, Giovanna Zambruno, Cristina Maria Failla

Research output: Contribution to journalArticle

Abstract

Vascular endothelial factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor for several growth factors of the VEGF family. Endothelial cells express a membrane-spanning form of VEGFR-1 and secrete a soluble variant of the receptor comprising only the extracellular region. The role of this variant has not yet been completely defined. In this study, we report that the secreted VEGFR-1 is present within the extracellular matrix deposited by endothelial cells in culture, suggesting a possible involvement in endothelial cell adhesion and migration. In adhesion assays, VEGFR-1 extracellular region specifically promoted endothelial cell attachment. VEGFR-1-mediated cell adhesion was divalent cation-dependent, and inhibited by antibodies directed against the α5β1 integrin. Moreover, VEGFR-1 promoted endothelial cell migration, and this effect was inhibited by anti-α5β1 antibodies. Direct binding of VEGFR-1 to the α5β1 integrin was also detected. Finally, binding to VEGFR-1 initiated endothelial cell spreading. Altogether these results indicate that the soluble VEGFR-1 secreted by endothelial cells becomes a matrix-associated protein that is able to interact with the α5β1 integrin, suggesting a new role of VEGFR-1 in angiogenesis, in addition to growth factor binding.

Original languageEnglish
Pages (from-to)3479-3489
Number of pages11
JournalJournal of Cell Science
Volume116
Issue number17
DOIs
Publication statusPublished - Sep 1 2003

Keywords

  • Angiogenesis
  • Integrin
  • Soluble receptor
  • VEGFR-1

ASJC Scopus subject areas

  • Cell Biology

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