Connective tissue growth factor is a positive regulator of epithelial-mesenchymal transition and promotes the adhesion with gastric cancer cells in human peritoneal mesothelial cells

Cytokine. 2013 Jan;61(1):173-80. doi: 10.1016/j.cyto.2012.09.013. Epub 2012 Oct 13.

Abstract

Connective tissue growth factor (CTGF) is involved in human cancer development and progression. Epithelial to mesenchymal transition (EMT) plays an important role in many biological processes. In this study, we wished to investigate the role of CTGF in EMT of peritoneal mesothelial cells and the effects of CTGF on adhesion of gastric cancer cells to mesothelial cells. Human peritoneal mesothelial cells (HPMCs) were cultured with TGF-β1 or various concentrations of CTGF for different time. The EMT process was monitored by morphology. Real-time RT-PCR and Western blot were used to evaluate the expression of vimentin, α-SMA , E-cadherin and β-catenin. RNA interference was used to achieve selective and specific knockdown of CTGF. We demonstrated that CTGF induced EMT of mesothelial cells in a dose- and time-dependent manner. HPMCs were exposed to TGF-β1 also underwent EMT which was associated with the induction of CTGF expression. Transfection with CTGF siRNA was able to reverse the EMT partially after treatment of TGF-β1. Moreover, the induced EMT of HPMCs was associated with an increased adhesion of gastric cancer cells to mesothelial cells. These findings suggest that CTGF is not only an important mediator but a potent activator of EMT in peritoneal mesothelial cells, which in turn promotes gastric cancer cell adhesion to peritoneum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Cadherins / biosynthesis
  • Cell Adhesion
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Connective Tissue Growth Factor* / genetics
  • Connective Tissue Growth Factor* / metabolism
  • Connective Tissue Growth Factor* / pharmacology
  • Disease Progression
  • Epithelial Cells / metabolism*
  • Epithelial-Mesenchymal Transition / genetics*
  • Epithelium / metabolism
  • Humans
  • Peritoneal Cavity / cytology
  • Peritoneum / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Stomach Neoplasms / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / pharmacology
  • Vimentin / biosynthesis
  • beta Catenin / biosynthesis

Substances

  • ACTA2 protein, human
  • Actins
  • Cadherins
  • RNA, Small Interfering
  • Transforming Growth Factor beta1
  • Vimentin
  • beta Catenin
  • Connective Tissue Growth Factor