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 α1(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 α1(I) and α2 chains on sodium dodecyl sulfate:polyacrylamide gel electrophoresis were found. Electrophoretogram analysis revealed further a dense band slightly slower than the α1(I) chain, most likely representing α1(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 α1(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.
This work was supported by Grant-in-Aid for Cancer Research 56-4 from the Ministry of Health and Welfare, Japan.