The significance of MMP-1 and MMP-2 in peritoneal disseminated metastasis of gastric cancer.
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.
Department of Surgery, Kurume University, School of Medicine, Fukuoka, Japan.
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K
Mizutani
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Kofuji
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K
Shirouzu
D018929:Cell Culture Techniques / Q000379:methods; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary*; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000502:physiology
D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1