Differential growth characteristics of low and high metastatic variant RAW117 murine lymphosarcoma cells

Abstract

The Abelson-virus-induced murine lymphosarcoma cell line RAW117-P and its in vivo selected highly malignant and metastatic variant RAW117-H10 have been studied for their growth in vivo, in vitro and in semi-solid agar. The highly malignant metastatic variant RAW117-H10 cells killed syngeneic Balb/c mice rapidly and formed 100-200 times more gross liver tumor nodules than the less malignant parental RAW117-P cells. On the other hand, there were no differences between the in vitro growth kinetics of these cells as measured by various parameters such as metaphase arrest or cells in DNA synthetic phase on various days after the initiation of the culture. These cells could be grown in semi-solid agar and formed characteristic colonies. The parental cells formed many very small colonies, whereas the highly malignant cells formed fewer, but very large colonies in soft agar. These results suggest that differential interactions of highly malignant RAW117-H10 cells with the host, particularly the host immune system, are much more important for regulating the number of metastases than any intrinsic growth advantages. It appears that growth differences, potentially based on lack of response to feedback inhibition rather than on kinetic parameters, are responsible for highly malignant RAW117-H10 cells forming larger colonies both in agar in vitro and in the liver in vivo.