Enhancement of metastatic and invasive capacity of gastric cancer cells by transforming growth factor-beta1

Acta Biochim Biophys Sin (Shanghai). 2006 Mar;38(3):179-86. doi: 10.1111/j.1745-7270.2006.00151.x.

Abstract

Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, exerts contradictory roles in different kinds of cells. A number of studies have revealed its involvement in the progression of many types of tumors. To investigate the effect of TGF-beta on gastric carcinoma, SGC7901, BGC823 and MKN28 (a TGF-beta-resistant cell line) adenocarcinoma clones were used. After pretreatment in serum-free medium with or without 10 ng/ml TGF-beta1, their experimental metastatic potential, chemotaxis, and invasive and adhesive ability were measured. Furthermore, zymography for gelatinase was processed. Liver colonies were also measured 4 weeks after inoculation of SGC7901, BGC823 and MKN28 in Balb/c nude mice, and an increase in the number of surface liver metastases was seen in SGC7901 (from 11.0+/-3.0 to 53.3+/-3.3) and BGC823 (from 9.3+/-2.5 to 60.0+/-2.8) groups, whereas there was no difference between MKN28 groups (from 35.2+/-3.8 to 38.5+/-2.7). In vitro experiments showed that TGF-beta1 increased the adhesion capacity of SGC7901 and BGC823 cells to immobilized reconstituted basement membrane/fibronectin matrices and promoted their penetration through reconstituted basement membrane barriers. Zymography demonstrated that enhanced invasive potential was partly due to the increased type IV collagenolytic (gelatinolytic) activity, but there was no difference in type IV collagenolytic activity and other biological behaviors between MKN28 groups. These results suggested that TGF-beta1 might modulate the metastatic potential of gastric cancer cells by promoting their ability to break down and penetrate basement membrane barriers and their adhesive and motile activities. We speculated that TGF-beta1 might act as a progression-enhancing factor in gastric cancer. Therefore blockage of TGF-beta or TGF-beta signaling might prevent gastric cancer cells from invading and metastasizing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Cell Adhesion / drug effects*
  • Cell Adhesion / physiology
  • Collagenases / analysis
  • Collagenases / metabolism
  • Fibronectins / metabolism
  • Gelatinases / analysis
  • Gelatinases / metabolism
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured

Substances

  • Fibronectins
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Collagenases
  • Gelatinases