Characteristics of a metastatic variant to the liver of human rectal adenocarcinoma cell line RCM-1.

The interaction of human rectal adenocarcinoma cell line RCM-1 cells with extracellular matrix components, was studied to elucidate the key steps in the liver metastasis of colorectal carcinomas. Highly metastatic variant L-10 cells selected from the metastatic foci of the liver after intrasplenic implantation in nude mice and its parental L-0 cells were used. L-10 cells showed a greater ability to adhere to laminin, fibronectin, and type I and type IV collagens than did L-0 cells but less haptotactic activity than that of L-0 cells to type I or type IV collagen, possibly due to the formation of cellular aggregates. In vitro invasion activities of both cell lines to basement membrane components (Matrigel) or type I collagen were minimal but enhanced by the addition of 12-O-tetradecanoylphorbol-13-acetate (TPA). L-10 cells showed greater ability to invade Matrigel than did L-0 cells, while L-0 cells exhibited higher activity in the invasion of type I collagen than did L-10 cells. TPA did not increase the production of metalloproteinases by both cells when analyzed by gelatin zymography. Based on the differences between the two cell lines, we postulated the following: (1) the high metastatic potential of L-10 cells was due to a greater capacity to attach to and cross the basement membrane; (2) TPA directly enhanced tumor cell invasiveness, not via the increased secretion of metalloproteinases; and (3) haptotactic migration had no significant correlation with the increased metastatic potential of L-10 cells.