Biosynthesis of an Interstitial Type of Collagen by Cloned Human Gastric Carcinoma Cells

In an attempt to elucidate the role played by neoplastic epithelial cells in the formation of stromal collagen, the synthesis of collagen by two cloned human gastric carcinoma cell lines was studied. The presence of antigenicity of procollagen alpha 1(I) chain in the cytoplasms of both carcinoma cell lines growing in culture was demonstrated by an immunocytochemical technique using specific antibodies. After denaturation of the radiolabeled collagenous proteins extracted from the combined cells and culture media, two components comigrating with authentic alpha 1(I) and alpha 2 chains on sodium dodecyl sulfate:polyacrylamide gel electrophoresis were found. Electrophoretogram analysis revealed further a dense band slightly slower than the alpha 1(I) chain, most likely representing alpha 1(I) trimer. These radioactive components disappeared after exposure of the samples to bacterial collagenase. The relative activity of collagen synthesis determined by using purified collagenase was slightly higher than that of fibroblasts derived from human synovial membrane in culture. The same antibodies to procollagen alpha 1(I) chain also labeled the cytoplasms of carcinoma cells, and extracellular matrix of the tumors developed after transplantation of one of the cell lines into the nude mice. Our data indicate that both human gastric carcinoma cell lines synthesize type 1 collagen in vivo as well as in vitro and suggest that carcinoma cells may play an active role in the formation of stromal collagen in most human carcinomas.