Changes of phenotypic characteristics of variants derived from Lewis lung carcinoma during long-term in vitro growth.

Two cultured cell clones derived from Lewis lung carcinoma (3LL), which have been shown to differ in their metastatic potential, were studied for their phenotypic stability in vitro. Several growth properties (lag-phase duration, doubling time, saturation density, cell shedding, plating efficiency) have been monitored for more than three years. The ability to induce primary tumors and metastasis, together with the response of cultured cells to adriamycin and bleomycin, have also been evaluated over the same period. The results show that the pattern of metastatic heterogeneity of the two clones is maintained during the serial passages in vitro, although the most actively metastatic clone (C108) displayed a reduced lung colony-forming ability at late passages. Furthermore, both clones exhibited an increasing sensitivity to adriamycin, while no changes were observed in the response to bleomycin. The present data suggest a phenotypic instability of tumor clones adapted to tissue culture conditions and, in particular, that the inherent chemosensitivity of tumor cells may change during long-term culture.