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

• Published in: European journal of cancer (1990) 2008-09, Vol.44 (13), p.1914-1921
• Main Authors: Lacal, Pedro M, Morea, Veronica, Ruffini, Federica, Orecchia, Angela, Dorio, Annalisa S, Failla, Cristina M, Soro, Simonetta, Tentori, Lucio, Zambruno, Giovanna, Graziani, Grazia, Tramontano, Anna, D’Atri, Stefania
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Biological and medical sciences; Cell Differentiation - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - physiology; Hematology, Oncology and Palliative Medicine; Humans; Medical sciences; Migration; Neovascularization, Pathologic - prevention & control; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Placenta Growth Factor; PlGF; Pregnancy Proteins - metabolism; Soluble VEGFR-1; Tumors; Umbilical Veins - blood supply; Vascular Endothelial Growth Factor Receptor-1 - physiology; VEGFR-1 activation; VEGFR-1 peptides
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2008.06.032

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.