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.
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