The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells
Metrics: PDF 1926 views | HTML 2437 views | ?
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.