SPARC is a key regulator of proliferation, apoptosis and invasion in human ovarian cancer

PLoS One. 2012;7(8):e42413. doi: 10.1371/journal.pone.0042413. Epub 2012 Aug 3.

Abstract

Background: Secreted protein acidic and rich in cysteine (SPARC), a calcium-binding matricellular glycoprotein, is implicated in the progression of many cancers. In this study, we investigated the expression and function of SPARC in ovarian cancer.

Methods: cDNA microarray analysis was performed to compare gene expression profiles of the highly invasive and the low invasive subclones derived from the SKOV3 human ovarian cancer cell line. Immunohistochemistry (IHC) staining was performed to investigate SPARC expression in a total of 140 ovarian tissue specimens. In functional assays, effects of SPARC knockdown on the biological behavior of ovarian cancer cells were investigated. The mechanisms of SPARC in ovarian cancer proliferation, apoptosis and invasion were also researched.

Results: SPARC was overexpressed in the highly invasive subclone compared with the low invasive subclone. High SPARC expression was associated with high stage, low differentiation, lymph node metastasis and poor prognosis of ovarian cancer. Knockdown of SPARC expression significantly suppressed ovarian cancer cell proliferation, induced cell apoptosis and inhibited cell invasion and metastasis.

Conclusion: SPARC is overexpressed in highly invasive subclone and ovarian cancer tissues and plays an important role in ovarian cancer growth, apoptosis and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neoplasm / immunology
  • Apoptosis* / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Female
  • G1 Phase / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lentivirus / metabolism
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Osteonectin / genetics
  • Osteonectin / metabolism*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology*
  • Ovary / metabolism
  • Ovary / pathology
  • Peptides / metabolism
  • RNA Interference
  • Reproducibility of Results
  • Resting Phase, Cell Cycle / genetics
  • Tumor Stem Cell Assay

Substances

  • Antibodies, Neoplasm
  • Osteonectin
  • Peptides

Grant support

This study was supported by a grant-in-aid for scientific research (2012TS088) from the Shandong University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.