A urokinase receptor-derived peptide inhibiting VEGF-dependent directional migration and vascular sprouting. (Articolo in rivista)

Type
Label
  • A urokinase receptor-derived peptide inhibiting VEGF-dependent directional migration and vascular sprouting. (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1158/1535-7163.MCT-13-0077 (literal)
Alternative label
  • Bifulco K, Longanesi-Cattani I, Liguori E, Arra C, Rea D, Masucci MT, De Rosa M, Pavone V, Stoppelli MP, Carriero MV. (2013)
    A urokinase receptor-derived peptide inhibiting VEGF-dependent directional migration and vascular sprouting.
    in Molecular cancer therapeutics
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Bifulco K, Longanesi-Cattani I, Liguori E, Arra C, Rea D, Masucci MT, De Rosa M, Pavone V, Stoppelli MP, Carriero MV. (literal)
Pagina inizio
  • 1981 (literal)
Pagina fine
  • 1983 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 12 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 10 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Experimental Oncology-National Cancer Institute of Naples, via M. Semmola, Naples 80131, Italy CNR - Istituto di Genetica e Biofisica \"ABT\" Via Pietro Castellino 111, Napoli, Italia (literal)
Titolo
  • A urokinase receptor-derived peptide inhibiting VEGF-dependent directional migration and vascular sprouting. (literal)
Abstract
  • The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration, and uPAR????? is the minimal sequence required to induce cell motility. We previously showed that soluble forms of uPAR elicit angiogenic responses through their uPAR????? chemotactic sequence and that the synthetic peptide SRSRY exerts similar effects. By a drug design approach, based on the conformational analysis of the uPAR????? sequence, we developed peptides (pERERY, RERY, and RERF) that potently inhibit signaling triggered by uPAR?????. In this study, we present evidence that these peptides are endowed also with a clear-cut antiangiogenic activity, although to different extents. The most active, RERF, prevents tube formation by human endothelial cells exposed to SRSRY. RERF also inhibits VEGF-triggered endothelial cell migration and cord-like formation in a dose-dependent manner, starting in the femtomolar range. RERF prevents F-actin polymerization, recruitment of ?v?3 integrin at focal adhesions, and ?v?3/VEGFR2 complex formation in endothelial cells exposed to VEGF. At molecular level, the inhibitory effect of RERF on VEGF signaling is shown by the decreased amount of phospho-FAK and phospho-Akt in VEGF-treated cells. In vivo, RERF prevents VEGF-dependent capillary sprouts originating from the host vessels that invaded angioreactors implanted in mice and neovascularization induced by subcorneal implantation of pellets containing VEGF in rabbits. Consistently, RERF reduced the growth and vascularization rate of tumors formed by HT1080 cells injected subcutaneously in the flanks of nude mice, indicating that RERF is a promising therapeutic agent for the control of diseases fuelled by excessive angiogenesis such as cancer. (literal)
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