http://www.cnr.it/ontology/cnr/individuo/prodotto/ID169232
Structure-based design of an urokinase-type plasminogen activator receptor-derived peptide inhibiting cell migration and lung metastasis (Articolo in rivista)
- Type
- Label
- Structure-based design of an urokinase-type plasminogen activator receptor-derived peptide inhibiting cell migration and lung metastasis (Articolo in rivista) (literal)
- Anno
- 2009-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1158/1535-7163.MCT-09-0174 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Maria Vincenza Carriero; Immacolata Longanesi-Cattani; Katia Bifulco; Ornella Maglio; Liliana Lista; Antonio Barbieri; Giuseppina Votta; Maria Teresa Masucci; Claudio Arra; Renato Franco; Mario De Rosa;
Maria Patrizia Stoppelli; Vincenzo Pavone. (literal)
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- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Departments of Experimental Oncology and Human Pathology, National Cancer Institute of Naples; Department of Chemistry, University of Naples \"Federico II\"; IBB-National Research Council; Institute of Genetics and Biophysics \"Adriano Buzzati-Traverso,\" National Research Council; Department of Experimental Medicine, Second University of Naples, Naples, Italy (literal)
- Titolo
- Structure-based design of an urokinase-type plasminogen activator receptor-derived peptide inhibiting cell migration and lung metastasis (literal)
- Abstract
- The urokinase-type plasminogen activator receptor (uPAR) plays a central role in sustaining the malignant phenotype and promoting tumor metastasis. The Ser88-Arg-Ser-Arg-Tyr92 is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as its ligand uPA. Here, we describe the generation of new peptide inhibitors of cell migration and invasion derived from
SRSRY by a drug design approach. Ac-Arg-Glu-Arg-Phe-NH2 (i.e., RERF), which adopts a turned structure in solution, was selected for its ability to potently prevent SRSRY-directed cell migration. Fluorescein-RERF associates with very high affinity to RBL-2H3 rat basophilic leukemia cells expressing the human formyl peptide receptor (FPR). Accordingly, femtomolar concentrations of RERF prevent agonist-dependent internalization of FPR and inhibit N-formyl-Met-Leu-Phe-dependent migration
in a dose-dependent manner. In the absence of FPR, fluorescein-RERF binds to cell surface at picomolar concentrations in an ?v integrin-dependent manner. The involvement of vitronectin receptor is further supported by the findings that 100 pmol/L RERF selectively inhibits vitronectin-dependent RBL-2H3 cell migration and prevents SRSRY-triggered uPAR/?v association. Furthermore, RERF reduces the speed of wound closure and the extent of Matrigel invasion by human fibrosarcoma HT1080 cells without affecting cell proliferation. Finally, a 3- to 5-fold reduction of lung metastasis number and size innude mice following i.v. injection of green fluorescent protein-expressing HT1080 cells in the presence of
3.32 mg/kg RERF is observed. Our findings indicate that RERF effectively prevents malignant cell invasion in vivo with no signs of toxicity and may represent a promising prototype drug for anticancer therapy. (literal)
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