Induction of gastric cancer cell adhesion through transforming growth factor-beta1-mediated peritoneal fibrosis

J Exp Clin Cancer Res. 2010 Oct 29;29(1):139. doi: 10.1186/1756-9966-29-139.

Abstract

Background: Peritoneal dissemination is one of the main causes of death in gastric cancer patients. Transforming growth factor-beta1 (TGF-β1), one of the most potent fibrotic stimuli for mesothelial cells, may play a key role in this processing. The purpose of this study is to elucidate the effects of TGF-β1 on regulation of gastric cancer adhesion to mesothelial cells.

Methods: Peritoneal tissues and peritoneal wash fluid were obtained for hematoxylin and eosin staining or ELISA to measure fibrosis and TGF-β1 levels, respectively. The peritoneal mesothelial cell line, HMrSV5, was used to determine the role of TGF-β1 in regulation of gastric cancer cell adhesion to mesothelial cells and expression of collagen, fibronectin, and Smad 2/3 by using adhesion assay, western blot, and RT-PCR.

Results: The data showed that TGF-β1 treatment was able to induce collagen III and fibronectin expression in the mesothelial cells, which was associated with an increased adhesion ability of gastric cancer cells, but knockdown of minimal sites of cell binding domain of extracellular matrix can partially inhibit these effects.

Conclusion: Peritoneal fibrosis induced by TGF-β1 may provide a favorable environment for the dissemination of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Adhesion*
  • Cell Line, Tumor
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epithelium / metabolism*
  • Epithelium / pathology
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Humans
  • Neoplasm Invasiveness
  • Peritoneal Fibrosis / genetics
  • Peritoneal Fibrosis / metabolism*
  • Peritoneal Fibrosis / pathology
  • Peritoneal Lavage
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / metabolism*
  • Peritoneal Neoplasms / secondary
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Staining and Labeling
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Collagen Type III
  • Fibronectins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta1