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, Maria Vincenza Carriero

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)54474-54487
Number of pages14
JournalOncotarget
Volume7
Issue number34
DOIs
Publication statusPublished - 2016

Keywords

  • Chondrosarcoma
  • Formyl peptide receptor type 1
  • Osteosarcoma
  • Peptides
  • Urokinase receptor

ASJC Scopus subject areas

  • Oncology

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