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 uPAR(88-92) sequence, since the DII(88-183) or DIIDIIR(88-284) uPAR domains retain motogen effect whereas DI(1-87) or DIII(184-284) domains, both lacking the uPAR(88-92) sequence, are ineffective.
Chondrosarcoma cells cross
matrigel in response to SuPAR, and their invasion capability is abrogated by RERF
peptide which inhibits uPAR(88-92) 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.