Research Papers:

The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells

Vincenzo Ingangi, Katia Bifulco, Ali Munaim Yousif, Concetta Ragone, Maria Letizia Motti, Domenica Rea, Michele Minopoli, Giovanni Botti, Giuseppe Scognamiglio, Flavio Fazioli, Michele Gallo, Annarosaria De Chiara, Claudio Arra, Paolo Grieco and Maria Vincenza Carriero _

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Oncotarget. 2016; 7:54474-54487. https://doi.org/10.18632/oncotarget.9976

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Vincenzo Ingangi1,2, Katia Bifulco1, Ali Munaim Yousif3, Concetta Ragone1,2, Maria Letizia Motti4, Domenica Rea5, Michele Minopoli1, Giovanni Botti1, Giuseppe Scognamiglio6, Flavio Fazioli7, Michele Gallo7, Annarosaria De Chiara6, Claudio Arra5, Paolo Grieco3, Maria Vincenza Carriero1

1Neoplastic Progression Unit, Department of Experimental Oncology, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy

2SUN Second University of Naples, Naples, Italy

3Department of Pharmacy, University Federico II, Naples, Italy

4University ‘Parthenope’, Naples, Italy

5Animal Facility, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy

6Pathology Unit, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy

7Surgery Unit, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy

Correspondence to:

Maria Vincenza Carriero, email: [email protected], [email protected]

Keywords: urokinase receptor, formyl peptide receptor type 1, osteosarcoma, chondrosarcoma, peptides

Received: April 18, 2016     Accepted: May 20, 2016     Published: June 13, 2016


The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88–92 is the minimal sequence required to induce cell motility and angiogenesis by interacting with the formyl peptide receptor type 1 (FPR1). In this study, we present evidence that the cyclization of the uPAR88–92 sequence generates a new potent inhibitor of migration, and extracellular matrix invasion of human osteosarcoma and chondrosarcoma cells expressing comparable levels of FPR1 on cell surface. In vitro, the cyclized peptide [SRSRY] prevents formation of capillary-like tubes by endothelial cells co-cultured with chondrosarcoma cells and trans-endothelial migration of osteosarcoma and chondrosarcoma cells. When chondrosarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density and circulating tumor cells in blood samples collected before the sacrifice, were significantly reduced in animals treated daily with i.p-administration of 6 mg/Kg [SRSRY] as compared to animals treated with vehicle only. Our findings indicate that [SRSRY] prevents three key events occurring during the metastatic process of osteosarcoma and chondrosarcoma cells: the extracellular matrix invasion, the formation of a capillary network and the entry into bloodstream.

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PII: 9976