[Pathogenesis and progression of scirrhous carcinoma].

The aim of the present paper is to elucidate the pathogenesis of gastric scirrhous carcinoma with special reference to fibrogenesis in cancer stroma and to the mode of cancer invasions. First, there are two hypotheses concerning the origin of the marked increase of collagen fibers in this type of carcinoma. One is thought to be production by fibroblasts stimulated by cancer cells; the other is synthesis by neoplastic cells. Our studies revealed that gastric cancer cells enhanced collagen production by fibroblasts in vitro, suggesting the contribution to the formation of stromal collagen in human gastric scirrhous cancer. However, one of four gastric scirrhous cancer cell lines, NKPS, was found to slightly from collagen fibers in the brain of the nude mouse. We also calculated the number of fibroblastic cells in gastric scirrhous and normal stroma by microscopical image analysis. The results showed that fibroblastic cells in scirrhous stroma were increased four-fold over those in normal stroma. This finding suggests that the mechanism by which fibrous stroma is produced in scirrhous carcinoma may be affected by the increased fibroblastic cells which were stimulated by many kinds of growth factors produced by cancer cells. It is also well known that the infiltrative growth and dispersion of scirrhous cancer cells within the gastric wall is very fast. To assess the mode of cancerous invasion of this carcinoma, we examined the urokinase-type plasminogen activator (uPA) activity of both types of cells (cancer cells and fibroblasts) with a coculture method. Scirrhous cancer cells enhanced production of uPA by fibroblasts. However, non-scirrhous gastric cancer cells produced much uPA by themselves. This finding suggests that scirrhous cancer cells can invade the gastric wall by use of uPA produced by enhanced fibroblasts, but that non-scirrhous cancer cells synthesize much uPA by themselves and can infiltrate the gastric wall.