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 t ransforming growth factor beta1 (TGF-beta1), secreted from tumour cell s, as a possible humoral factor which functions in a paracrine manner to stimulate the production of collagen in regional fibroblasts. Immun ohistochemical staining revealed that tumour cells in scirrhous carcin omas 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 rela tively strong signals compared with those from non-scirrhous carcinoma (MKN-28 and MKN-45). In the culture media of scirrhous carcinoma cell s, the active form of TGF-beta1 was detected, while in those of the no n-scirrhous carcinoma cells the latent form was demonstrated by both c olony and radioreceptor assays. The culture medium from KATO-III showe d strong stimulating activity of collagen synthesis in fibroblasts, an d this activity was partially neutralised by an anti-TGF-beta1 antibod y. These results suggest that tumour cells in scirrhous carcinoma prod uce more active-form TGF-beta1 than does non-scirrhous carcinoma and t hus is partially responsible for the observed enhanced collagen deposi tion in the region.