Effects of transforming growth factor-beta released from gastric carcinoma cells on the contraction of collagen-matrix gels containing fibroblasts.

To investigate the mechanisms underlying contraction of the stomach wall in cases of gastric scirrhous carcinoma, we have developed an in vitro model for gastric cancer, in which both fibroblasts and gastric carcinoma cells are embedded within a collagen matrix. Gastric carcinoma cells of the scirrhous type (KATO-III) but not the nonscirrhous type (MKN-28) markedly enhanced the ability of human intestine, human lip, and mouse kidney fibroblasts to contract collagen gels. KATO-III cells released transforming growth factor-beta (TGF-beta) into culture media in an activated form, whereas the MKN-28 cells produced a latent form. The role of TGF-beta produced by gastric cancer cells from the scirrhous type was clarified by adding TGF-beta (receptor grade) into collagen gels embedded with fibroblasts, contraction being enhanced. Other growth factors tested, including transforming growth factor-alpha and epidermal growth factor, did not enhance the contraction of collagen gels containing embedded human and rodent fibroblasts. These results suggest that the activated form of TGF-beta released from gastric scirrhous carcinoma cells stimulates fibroblasts to contract the collagenous stroma of the stomach wall, which leads to the so-called "linitis plastica" stomach condition.