Inverse correlation of collagen production to anchorage independence and tumorigenicity in W8- and M-cell lines

Collagen production by fibroblasts has been shown to be transformation sensitive and to correlate inversely with tumorigenicity. Therefore, it is of interest to determine if carcinoma cell collagen production is similar to fibroblast collagen production. Since there are few carcinoma model systems available for this study that have cultured cells with increasing tumorigenic potential, a new series of cell lines, referred to as M-cells, were developed from the well-described rat liver epithelial cell line W8, originally established by I. B. Weinstein. The W8 cell line is a N-acetoxy-2-acetylaminofluorene-treated, weakly tumorigenic rat liver cell derived from the parent K16 cell line. The M-cells were serially selected by isolating cell lines from tumors and reinjecting them into animals. Although these M-cells maintain their epithelial characteristics, their overall protein production, their type of collagen, and their ability to form undifferentiated carcinomas in vivo, they progressively exhibit increasing tumorigenic potential, increasing anchorage independence, and decreasing collagen production. The W8 and M-cells maintain decreasing amounts of collagen type I trimer production, which most likely contributes to the decreasing connective tissue stroma observed in their carcinomas. This cell system provides a new model to examine epithelial cell surface and extracellular substrate attachment interactions.