title: Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for the alpha 5 beta 1 integrin.
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 alpha 5 beta 1 integrin. Moreover, VEGFR-1 promoted endothelial cell migration, and this effect was inhibited by anti-alpha 5 beta 1 antibodies. Direct binding of VEGFR-1 to the alpha 5 beta 1 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 alpha 5 beta 1 integrin, suggesting a new role of VEGFR-1 in angiogenesis, in addition to growth factor binding.
authors.affiliation: Molecular and Cell Biology Laboratory, IDI-IRCCS, via Monti di Creta 104, 00167 Rome, Italy. a.orecchia@idi.it
authors.forename: Angela
authors.initials: A
authors.lastname: Orecchia
authors.forename: Pedro Miguel
authors.initials: PM
authors.lastname: Lacal
authors.forename: Cataldo
authors.initials: C
authors.lastname: Schietroma
authors.forename: Veronica
authors.initials: V
authors.lastname: Morea
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Failla
mesh_terms: D000595:Amino Acid Sequence; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008024:Ligands; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D020539:Sequence Analysis, Protein; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D002413:Cations, Divalent; D005353:Fibronectins; D039081:Integrin alpha5beta1; D008024:Ligands; D020033:Protein Isoforms; D040281:Vascular Endothelial Growth Factor Receptor-1