Gastric cancer cell supernatant causes apoptosis and fibrosis in the peritoneal tissues and results in an environment favorable to peritoneal metastases, in vitro and in vivo

BMC Gastroenterol. 2012 Apr 20:12:34. doi: 10.1186/1471-230X-12-34.

Abstract

Background: In this study, we examined effects of soluble factors released by gastric cancer cells on peritoneal mesothelial cells in vitro and in vivo.

Methods: HMrSV5, a human peritoneal mesothelial cell line, was incubated with supernatants from gastric cancer cells. Morphological changes of HMrSV5 cells were observed. Apoptosis of HMrSV5 cells was observed under a transmission electron microscope and quantitatively determined by MTT assay and flow cytometry. Expressions of apoptosis-related proteins (caspase-3, caspase-8, Bax, bcl-2) were immunochemically evaluated.

Results: Conspicuous morphological changes indicating apoptosis were observed in HMrSV5 cells 24 h after treatment with the supernatants of gastric cancer cells. In vivo, peritoneal tissues treated with gastric cancer cell supernatant were substantially thickened and contained extensive fibrosis.

Conclusions: These findings demonstrate that supernatants of gastric cancer cells can induce apoptosis and fibrosis in HMrSV5 human peritoneal mesothelial cells through supernatants in the early peritoneal metastasis, in a time-dependent manner, and indicate that soluble factors in the peritoneal cavity affect the morphology and function of mesothelial cells so that the resulting environment can become favorable to peritoneal metastases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology*
  • Fibrosis
  • Humans
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Peritoneal Neoplasms / secondary*
  • Peritoneum / drug effects*
  • Peritoneum / metabolism
  • Peritoneum / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stomach Neoplasms / metabolism*
  • Time Factors
  • bcl-2-Associated X Protein / metabolism

Substances

  • Culture Media, Conditioned
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Caspase 3
  • Caspase 8