Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination

Mol Cancer. 2011 Sep 28:10:122. doi: 10.1186/1476-4598-10-122.

Abstract

Background: Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown.

Results: In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P < 0.05). Patients with positive CTGF expression had significantly lower cumulative postoperative 5 year survival rate than those with negative CTGF expression (22.9% versus 48.1%, P < 0.001). We demonstrated that knockdown of CTGF expression significantly inhibited cell growth of gastric cancer cells and decreased cyclin D1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines.

Conclusions: These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism*
  • Down-Regulation*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary*
  • RNA Interference
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology

Substances

  • Connective Tissue Growth Factor