Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for theα5β1 integrin
Author:
Orecchia Angela1, Lacal Pedro Miguel2, Schietroma Cataldo1, Morea Veronica3, Zambruno Giovanna1, Failla Cristina Maria1
Affiliation:
1. Molecular and Cell Biology Laboratory, IDI-IRCCS, via Monti di Creta 104,00167 Rome, Italy 2. Pharmacology Laboratory, IDI-IRCCS, via Monti di Creta 104, 00167 Rome,Italy 3. Laboratory of Molecular Biology, MRC Centre, Hills Road, Cambridge CB2 2QH,UK, and CNR Center of Molecular Biology, c/o Department of Biochemical Sciences, University of Rome 'La Sapienza', P.le A. Moro 5, 00185 Rome,Italy
Abstract
Vascular endothelial growth 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 theα5β1 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.
Publisher
The Company of Biologists
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