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  • Title: Targeting of human renal tumor-derived endothelial cells with peptides obtained by phage display.
    Author: Bussolati B, Grange C, Tei L, Deregibus MC, Ercolani M, Aime S, Camussi G.
    Journal: J Mol Med (Berl); 2007 Aug; 85(8):897-906. PubMed ID: 17384922.
    Abstract:
    The phenotypic and molecular diversity of tumor-associated vasculature provides a basis for the development of targeted diagnostics and therapeutics. In the present study, we have developed a peptide-based targeting of human tumor endothelial cells (TEC) derived from renal carcinomas. We used a murine model of human tumor angiogenesis, in which TEC injected subcutaneously in severe combined immunodeficiency (SCID) mice organized in vascular structures connected with the mouse circulation, to screen in vivo a phage display library of random peptides. Using this approach, we identified cyclic peptides showing specific binding to TEC and not to normal human endothelial cells or to murine tumor endothelial cells. In particular, the peptide CVGNDNSSC (BB1) bound to TEC in vitro and in vivo. Using BB1 peptide conjugated with the ribosome-inactivating toxin saporin, we targeted TEC in vivo. Injection of BB1-saporin but not saporin alone or control modified BB-1ala saporin induced a selective cell apoptosis and disruption of the TEC vessel network. No increase in cell apoptosis was found in other murine organs. In conclusion, the identification of peptide sequences able to bind selectively human tumor-derived endothelial cells may represent a tool to deliver antiangiogenic or antitumor agents within the neoplastic vessels.
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