Immunohistochemical study of collagen synthesis in an in-vitro model of scirrhous carcinoma of the stomach.

Objective: The mechanisms involved in the unique stromal change that occurs upon cancer invasion are poorly understood in scirrhous carcinoma of the stomach.

Methods: Three different human gastric cancer cell lines (KATO-III, MKN-28, MKN-45) and human fibroblast cells (TIG-101) were co-cultured three-dimensionally in collagen gels. The gels, in vitro models of gastric cancer, were immunostained by monoclonal antibodies to human placental prolyl 4-hydroxylase (PH, a key enzyme of collagen synthesis) and then examined by light and electron microscopy.

Results: Under co-culture of cancer cells and fibroblasts, cytoplasmic staining for PH was observed in both the cancer cells (KATO-III, MKN-28, MKN-45) and fibroblasts. No significant difference in the expression patterns of the alpha- and beta-subunits of PH was observed not only among the KATO-III, MKN-28 and MKN-45 cell lines but also between cancer cells and fibroblasts.

Conclusions: These findings indicate that both cancer cells and fibroblasts can synthesize collagen in gastric cancer models. Moreover, this property may not be a unique characteristic of scirrhous gastric cancer cells, but common to gastric cancer cells and fibroblasts in vitro.