The significance of MMP-1 and MMP-2 in peritoneal disseminated metastasis of gastric cancer

Surg Today. 2000;30(7):614-21. doi: 10.1007/s005950070101.

Abstract

The purpose of this study was to clarify the role of the matrix metalloproteinases (MMPs), collagenase (MMP-1), and gelatinase A (MMP-2), both of which are known to be involved in the development of gastric cancer, in peritoneal dissemination. The concentrations of MMP-1 and MMP-2 in the supernatant of mixed culture simulated peritoneal dissemination were measured in vitro with mesothelial cells and cancer cells using an enzyme-linked immunosorbent assay. The concentration of MMP-1 increased significantly after the contact culture was mixed with these two cells, in comparison with the non-contact mixed culture or the mesothelial cell culture alone. These results demonstrate that the production of MMP-1 derived from mesothelial cells was increased by contact with cancer cells. To clarify the effect of MMP-1 and MMP-2 on gastric cancer invasion, an invasion assay using matrigel was performed. After treatment with anti-MMP-1 monoclonal antibody (mAb) or anti-MMP-2 mAb, the number of matrigel-penetrating cancer cells was significantly reduced, indicating that MMP-1 and MMP-2 derived from mesothelial cells had a strong reaction to gastric cancer invasion. In conclusion, as MMP-1 showed a paracrine-like action responding to stimulus from cancer cells, it seemed to play an important role in the progression of peritoneal dissemination.

MeSH terms

  • Cell Culture Techniques / methods
  • Humans
  • Matrix Metalloproteinase 1 / analysis
  • Matrix Metalloproteinase 1 / pharmacology*
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 2 / pharmacology*
  • Neoplasm Invasiveness
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary*
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured / physiology

Substances

  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1