Important Role of Stromal Cells in the Spreading of Gastrointestinal Tract Carcinomas -From the Aspect of Breakdown of Extracellular Matrix-

Yoshihide Otani, Yoshihiko Sakurai**, Naoki Igarashi, Takeyoshi Yokoyama, Masaru Kimata, Kaori Kameyama*, Tetsuro Kubota, Koichiro Kumai, Masaki Kitajima

Departments of Surgery and Pathology*, School of Medicine, Keio University
Department of Surgery**, National Tochigi Hospital

We have investigated the role of stromal cells in the invasion and metastasis of gastrointestinal tract carcinomas. The extracellular matrix is degraded by a carcinoma during its spread, which is known to be caused by matrix metalloproteinases (MMPs). We observed the gene expression of MMP-1 by in situ hybridization in gastric and colorectal carcinomas and found that MMP-1 mRNA was expressed in the stromal cells and some inflammatory cells. A human gastric carcinoma cell line, MKN74, was co-cultured with human fibroblasts, resulting greater MMP-1 production than in the simple culture. Another gastric carcinoma cell line, TMK-1, was injected intraperitoneally into BALB/c nu/nu mice along with the conditioned medium of a human fibroblast culture. Five weeks after the injection the mice were sacrificed and the nodules resulting from peritoneal dissemination were counted. The carcinoma cells with fibroblast-conditioned medium formed more nodules than the carcinoma cells without it (p<0.05). On the basis of these obervations, we can speculate that the stromal cells play important roles during invasion and metastasis and also that the stromal cells affect the degree of malignancy of the tumor.

Key words
stromal cells, invasion and metastasis of gastrointestinal carcinoma, matrix metalloproteinase

Reprint requests
Yoshihide Otani Department of Surgery, School of Medicine, Keio University
35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 JAPAN

Accepted
December 3, 1997

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