Potentiation of gastric carcinoma cell invasion by TNF‐α and MMP secretion from peritoneal mesothelial cells

Abstract

Adhesion and invasion of gastric carcinoma cells to the peritoneum are crucial processes of metastatic dissemination. These processes involve a variety of factors including cell adhesion molecules and cytokines, and are promoted by inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α). In this study, we utilized reconstituted peritoneal membranes consisting of Matrigel and peritoneal mesothelial cells in the Boyden chamber system to examine effects of TNF‐α on carcinoma cell migration. The transmigration of MKN1 human gastric carcinoma cells through reconstituted peritoneal membranes was potentiated in the presence of TNF‐α. TNF‐α also promoted integrin‐meditated adhesion of MKN1 cells to monolayers of mesothelial cells. We then analyzed matrix metalloproteinase (MMP) production by gelatin zymography, and found that both MKN1 cells and mesothelial cells secreted higher levels of MMP‐2 and MMP‐9 upon the treatment of these cells with TNF‐α. These results suggest that the secretion of MMPs stimulated by TNF‐α plays an important role in the peritoneal invasion of gastric cancer.