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 beta 1 (TGF-beta 1), 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-beta 1 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-beta 1 antibody. These results suggest that tumour cells in
scirrhous carcinoma produce more active-form
TGF-beta 1 than does non-
scirrhous carcinoma and thus is partially responsible for the observed enhanced
collagen deposition in the region.