Involvement of the soluble urokinase receptor in chondrosarcoma cell mobilization

Maria Vincenza Carriero, Katia Bifulco, Immacolata Longanesi-Cattani, Maria Teresa Masucci, Annarosaria De Chiara, Flavio Fazioli, Gioconda Di Carluccio, Giuseppe Pirozzi, Michele Gallo, Antonello La Rocca, Gaetano Apice, Gaetano Rocco

Research output: Contribution to journalArticle

Abstract

High levels of urokinase receptor (uPAR) in tissue and serum of patients with chondrosarcoma correlate with poor prognosis. First, we analyzed the uPAR levels in tissues and plasma of five patients affected by chondrosarcoma. Interestingly, very high levels of uPAR and its soluble forms (SuPAR) were found on tumor cell surfaces and plasma, respectively, of two patients with lung metastases. Therefore, to investigate the role of SuPAR in chondrosaromas, we generated a primary cell culture from a chondrosarcoma tissue overexpressing uPAR on cell surfaces. We found that chondrosarcoma-like primary culture cells release a large amount of SuPAR in the medium. In vitro, SuPAR elicits chondrosarcoma cell migration likely through its uPAR88-92 sequence, since the DII88-183 or DIIDIIR88-284 uPAR domains retain motogen effect whereas DI1-87 or DIII184-284 domains, both lacking the uPAR88-92 sequence, are ineffective. Chondrosarcoma cells cross matrigel in response to SuPAR, and their invasion capability is abrogated by RERF peptide which inhibits uPAR88-92 signalling. These findings assign a role to uPAR in mobilizing chondrosarcoma cells and suggest that RERF peptide may be regarded as a prototype to generate new therapeutics for the chondrosarcoma treatment.

Original languageEnglish
Article number842842
JournalSarcoma
Volume2011
DOIs
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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