THE EXPRESSION OF THE SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE (SPARC) IS ASSOCIATED WITH THE NEOPLASTIC PROGRESSION OF HUMAN-MELANOMA

SPARC (secreted protein acidic and rich in cysteine) is an extracellul ar protein associated with tissues exhibiting high rates of cell proli feration and matrix remodeling, The current work shows that the human melanoma cell lines IIB-MEL-LES, IIB-MEL-IAN, and IIB-MEL-J and differ ent human metastatic melanomas expressed high levels of SPARC mRNA and protein, By western blot analysis we detected a single secreted 42-kD a band in human diploid fibroblasts-conditioned medium and a 45-to 40- kDa doublet in the three melanoma cell lines and all the metastatic me lanomas tested, Part of the melanoma samples and cell lines showed an additional doublet of 36-34 kDa, SPARC mRNA was expressed by the three established cell lines, 14 metastatic melanoma samples, and tumors ra ised in nude mice, and no spliced variants were found, The heterogeneo us pattern of SPARC secreted by human melanoma cells is the result of post-translational glycosylation and a specific extracellular leupepti n-inhibitable cleavage. Unlike human fibroblasts, melanoma cells did n ot overexpress SPARC on addition of TGF-beta. Immunohistochemical anal ysis showed that SPARC was strongly expressed in 100% of primary melan omas (7 of 7) and metastatic melanomas (29 of 29), moderately expresse d inmost of the positive dysplastic nevi (13 of 14), and only weakly e xpressed in nevocellular nevi (4 of 25), Normal melanocytes did not ex press SPARC, The data suggest that the expression of SPARC is associat ed with the neoplastic progression of human melanoma.