TRANSFORMING GROWTH-FACTOR-BETA-1 SECRETED FROM SCIRRHOUS GASTRIC-CANCER CELLS IS ASSOCIATED WITH EXCESS COLLAGEN DEPOSITION IN THE TISSUE

To explore the mechanism of increased collagen deposition in scirrhous carcinoma of the stomach, an attempt was made to define the role of transforming growth factor beta1 (TGF-beta1), secreted from tumour cells, as a possible humoral factor which functions in a paracrine manner to stimulate the production of collagen in regional fibroblasts. Immunohistochemical staining revealed that tumour cells in scirrhous carcinomas were generally stained more intensively than those in other types of carcinomas. On Northern blot analysis the tumour cells established from scirrhous carcinoma (KATO-III, OCUM-1 and HSC-39) exhibited relatively strong signals compared with those from non-scirrhous carcinoma (MKN-28 and MKN-45). In the culture media of scirrhous carcinoma cells, the active form of TGF-beta1 was detected, while in those of the non-scirrhous carcinoma cells the latent form was demonstrated by both colony and radioreceptor assays. The culture medium from KATO-III showed strong stimulating activity of collagen synthesis in fibroblasts, and this activity was partially neutralised by an anti-TGF-beta1 antibody. These results suggest that tumour cells in scirrhous carcinoma produce more active-form TGF-beta1 than does non-scirrhous carcinoma and thus is partially responsible for the observed enhanced collagen deposition in the region.