Enhancement of metastatic capacity of fibroblast-tumor cell interaction in mice.

A low metastatic clone, G6, was isolated from the B16 melanoma cell line by cloning procedure. When the cells were cultured in vitro with fibroblasts from newborn mice, the lung-colonizing potential of G6 cells was substantially increased. The effect of coculture depended on the number of the fibroblasts. The elevated colonizing potential of G6 cells was reversed to the original low potential by subculturing them for 20 days without the fibroblasts. The culture medium conditioned by G6-fibroblast coculture demonstrated an activity to enhance the lung-colonizing potential of G6 cells, whereas the medium from the culture of fibroblasts alone showed only a little activity. The growth rate and plating efficiency of G6 cells cultured with the fibroblasts or in the conditioned medium did not differ from those of uncocultured G6 cells. The potentiating activity in the conditioned medium was nondialyzable and stable to heating at 80 degrees C for 10 min, but was lost after heating for 10 min at 120 degrees C, or by the treatment with trypsin. These results indicate that the enhancement of lung-colonizing potential of G6 cells could be mediated by a soluble factor(s) released from cocultured fibroblasts.