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Sarcoma
Volume 2011, Article ID 842842, 10 pages
http://dx.doi.org/10.1155/2011/842842
Research Article

Involvement of the Soluble Urokinase Receptor in Chondrosarcoma Cell Mobilization

1Department of Experimental Oncology, National Cancer Institute of Naples, Via Mariano Semmola 1, 80131 Naples, Italy
2Department of Human Pathology, National Cancer Institute of Naples, Via Mariano Semmola 1, 80131 Naples, Italy
3Department of Surgical Oncology, National Cancer Institute of Naples, Via Mariano Semmola 1, 80131 Naples, Italy
4Department of Medical Oncology, National Cancer Institute of Naples, Via Mariano Semmola 1, 80131 Naples, Italy

Received 26 August 2010; Revised 3 November 2010; Accepted 1 December 2010

Academic Editor: Charles Scoggins

Copyright © 2011 Katia Bifulco et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.