Sarcomatous Change and Maintenance of Differentiation in Long-Term Cultures of Mouse Mammary Carcinoma

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Abstract
This study had 2 objectives: 1) to follow the behavior in vitro of cells cultured from C3H mouse mammary carcinomas with respect to maintenance of differentiation as assayed in vivo and 2) to supply additional evidence regarding the “sarcomatous” transformation which epithelial tumors frequently undergo and which appeared in cell strains of this study. Cell strains were established in culture from 18 different tumors of mammary-gland origin. Cells cultured in a serumembyro extract medium and transferred from culture to mice during the first 5 months in vitro grew as differentiated mammary carcinomas, but cells transferred after this period produced sarcoma-like tumors. Experimental evidence indicated that the “sarcomatous” changes in the various cell strains resulted from two entirely different phenomena: 1) neoplastic transformation of stromal cells in culture, and 2) morphologic alteration of carcinoma cells to resemble sarcoma cells of connective-tissue origin. One strain cultured from the long-transplanted C3HBA mammary carcinoma and grown in serum-supplemented chemically defined medium continued to reproduce in mice the epithelial glandular architecture of the original tumor after 1½ years and 35 transplant generations of growth in vitro. The high arginase activity characteristic of C3H mammary carcinomas was also maintained. Apparently two factors accounted for the maintenance of recognizable differentiation in cells of this strain: 1) the type of culture medium used, and 2) the stabilization of tumor morphology and differentiation during numerous passages in vivo before explantation of tumor tissue to culture.

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