SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells

Gary K. Yiu, Wood Yee Chan, Shu Wing Ng, Pui Suen Chan, Kwok Kuen Cheung, Ross S. Berkowitz, Samuel C. Mok

Research output: Journal article publicationJournal articleAcademic researchpeer-review

175 Citations (Scopus)

Abstract

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular Ca2+-binding matricellular glycoprotein that associates with cell populations undergoing migration, morphogenesis, and differentiation. Studies on endothelial cells have established that its principal functions in vitro are counteradhesion and antiproliferation. The mechanism(s) underlying these antitumor effects is unknown. In this study, we showed that SPARC expression in ovarian cancer cells is inversely correlated with the degree of malignancy. The immunohistochemical data presented here confirmed the importance of diminished SPARC expression in ovarian cancer development. Treating human ovarian surface epithelial cells and ovarian cancer cells with SPARC revealed that as SPARC inhibits the proliferation of both normal and cancer cells, it induces apoptosis only in cancer cells. This observation indicates that down-regulation of SPARC is essential for ovarian carcinogenesis as cancer cells become sensitized to the apoptotic activity of SPARC during malignant transformation. We also showed here the first direct evidence that putative SPARC receptors are present on ovarian epithelial cells. Their levels are higher in human ovarian surface epithelial cells than cancer cells. Binding of SPARC to its receptor is likely to trigger tissue-specific signaling pathways that mediate its tumor suppressing functions. Decrease in ligand-receptor interaction by the down-regulation of SPARC and/or its receptor is essential for ovarian carcinogenesis.

Original languageEnglish
Article number61732
Pages (from-to)609-622
Number of pages14
JournalAmerican Journal of Pathology
Volume159
Issue number2
DOIs
Publication statusPublished - 1 Jan 2001
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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