The expression of the secreted protein acidic and rich in cysteine neoplastic progression of human melanoma

Fernanda Ledda, Alicia I. Bravo, Soraya Adris, Laura Bover, José Mordoh, Osvaldo L. Podhajcer

Research output: Contribution to journalArticlepeer-review

152 Scopus citations

Abstract

SPARC (secreted protein acidic and rich in cysteine) is an extracellular protein associated with tissues exhibiting high rates of cell proliferation and matrix remodeling. The current work shows that the human melanoma cell lines IIB-MEL-LES, IIB-MEL-IAN, and IIB-MEL-J and different human metastatic melanomas expressed high levels of SPARC mRNA and protein. By western blot analysis we detected a single secreted 42-kDa band in human diploid fibroblasts-conditioned medium and a 45-to 40-kDa doublet in the three melanoma lines and all the metastatic melanomas 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 raised in nude mice, and no spliced variants were found. The heterogeneous pattern of SPARC secreted by human melanoma cells is the result of post-translational glycosylation and a specific extracellular leupeptin-inhibitable cleavage. Unlike human fibroblasts, melanoma cells did not overexpress SPARC on addition of TGF-β. Immunohistochemical analysis showed that SPARC was strongly expressed in 100% of primary melanomas (7 of 7) and metastatic melanomas (29 of 29), moderately expressed in most of the positive dysplastic nevi (13 of 14), and only weakly expressed in nevocellular nevi (4 of 25). Normal melanocytes did not express SPARC. The data suggest that the expression of SPARC is associated with the neoplastic progression of human melanoma.

Original languageEnglish (US)
Pages (from-to)210-214
Number of pages5
JournalJournal of Investigative Dermatology
Volume108
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Extracellular matrix
  • Stromal
  • Tumor cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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