title: Inhibition of endothelial cell migration and angiogenesis by a vascular endothelial growth factor receptor-1 derived peptide.
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.
authors.affiliation: Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy. p.lacal@idi.it
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Lacal
authors.forename: Veronica
authors.initials: V
authors.lastname: Morea
authors.forename: Federica
authors.initials: F
authors.lastname: Ruffini
authors.forename: Angela
authors.initials: A
authors.lastname: Orecchia
authors.forename: Annalisa S
authors.initials: AS
authors.lastname: Dorio
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Failla
authors.forename: Simonetta
authors.initials: S
authors.lastname: Soro
authors.forename: Lucio
authors.initials: L
authors.lastname: Tentori
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Grazia
authors.initials: G
authors.lastname: Graziani
authors.forename: Anna
authors.initials: A
authors.lastname: Tramontano
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Atri
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010446:Peptide Fragments / Q000494:pharmacology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism; D014471:Umbilical Veins / Q000098:blood supply*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology*
chemical_list: D020533:Angiogenesis Inhibitors; C000608036:PGF protein, human; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1