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 vascular endothelial growth factor-A (VEGF-A) and placenta growth factor (PlGF), whereas the biological function of sVEGFR-1 has not been fully elucidated. We recently reported that sVEGFR-1 induces endothelial cell motility and promotes endothelial cell adhesion through the interaction with α5β1 integrin. In this study, we tested a set of VEGFR-1 derived peptides for their ability to block sVEGFR-1-induced migration of endothelial cells. Peptide B3 was found to specifically inhibit cell migration induced by sVEGFR-1 and mVEGFR-1-specific ligands, such as PlGF and VEGF-B. Amino acid Thr161 in peptide B3 sequence resulted indispensable for this inhibitory activity and also Ser162 was required for a full inhibitory activity. Moreover, peptide B3 markedly hampered angiogenesis in vitro (formation of tubule-like structures in collagen gels) and in vivo (matrigel-plug assay in mice). Peptide B3 was found to interact with the extracellular region of mVEGFR-1 common to sVEGFR-1, and to interfere with dimerisation of the receptor. 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. Supported by the Italian Ministry of Health, by “Compagnia di San Paolo” and by the National Council of Research.
Lacal, P., Morea, V., Ruffini, F., Orecchia, A., Failla, C., Dorio, A., et al. (2007). VEGFR-1 derived peptide specifically inhibits PlGF and VEGF-B-induced migration of endothelial cells and in vivo angiogenesis.. In Proceedings of the 49° Congresso della Società Italiana di Cancerologia.
VEGFR-1 derived peptide specifically inhibits PlGF and VEGF-B-induced migration of endothelial cells and in vivo angiogenesis.
TENTORI, LUCIO;GRAZIANI, GRAZIA;
2007-01-01
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 vascular endothelial growth factor-A (VEGF-A) and placenta growth factor (PlGF), whereas the biological function of sVEGFR-1 has not been fully elucidated. We recently reported that sVEGFR-1 induces endothelial cell motility and promotes endothelial cell adhesion through the interaction with α5β1 integrin. In this study, we tested a set of VEGFR-1 derived peptides for their ability to block sVEGFR-1-induced migration of endothelial cells. Peptide B3 was found to specifically inhibit cell migration induced by sVEGFR-1 and mVEGFR-1-specific ligands, such as PlGF and VEGF-B. Amino acid Thr161 in peptide B3 sequence resulted indispensable for this inhibitory activity and also Ser162 was required for a full inhibitory activity. Moreover, peptide B3 markedly hampered angiogenesis in vitro (formation of tubule-like structures in collagen gels) and in vivo (matrigel-plug assay in mice). Peptide B3 was found to interact with the extracellular region of mVEGFR-1 common to sVEGFR-1, and to interfere with dimerisation of the receptor. 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. Supported by the Italian Ministry of Health, by “Compagnia di San Paolo” and by the National Council of Research.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
