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Aberrant promoter methylation of SPARC in ovarian cancer

Matthew J Socha1, Neveen Said, Yanshan Dai

  • 1Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.

Neoplasia (New York, N.Y.)
|January 30, 2009
PubMed

Insights

Secreted protein acidic and rich in cysteine (SPARC) is epigenetically silenced in ovarian cancer, leading to decreased expression. Restoring SPARC inhibits cancer cell proliferation, suggesting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Epigenetic silencing of tumor suppressor genes is crucial in carcinoma development.
  • Secreted protein acidic and rich in cysteine (SPARC) inhibits ovarian cancer cell growth and is epigenetically silenced in various cancers.

Purpose of the Study:

  • To investigate if SPARC is downregulated in ovarian cancer via aberrant promoter hypermethylation.
  • To explore the potential of SPARC as a biomarker and therapeutic target in ovarian carcinomas.

Main Methods:

  • Analysis of SPARC expression in ovarian cancer cell lines.
  • Methylation-specific polymerase chain reaction to assess Sparc promoter methylation status.
  • Treatment with 5-aza-2'-deoxycytidine and SPARC reintroduction to evaluate functional effects.

Main Results:

  • SPARC mRNA expression was decreased or absent in most ovarian cancer cell lines studied.
  • Hypermethylation of the Sparc promoter correlated with reduced SPARC expression.
  • Demethylation treatment and SPARC reintroduction inhibited ovarian cancer cell proliferation.
  • Sparc promoter methylation was detected in 68% of primary ovarian tumors, with decreased SPARC protein levels in higher-grade cancers.

Conclusions:

  • Aberrant promoter hypermethylation of SPARC is a significant factor in ovarian carcinoma development and survival.
  • SPARC re-expression can suppress ovarian cancer cell proliferation.
  • SPARC methylation status and expression levels may serve as a biomarker for ovarian cancer progression.
  • SPARC represents a potential therapeutic target for ovarian cancer treatment.

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