FREQUENCY OF METASTASIS IN SYRIAN-HAMSTER TUMOR-CELLS SELECTED FOR LOW-LEVELS OF TYPICAL MULTIDRUG-RESISTANCE

The metastatic capability of cells at the initial stages of selection for ''typical'' (P-glycoprotein-mediated) multidrug resistance (MDR) was studied. Two independent sublines, 2SC/4-1 and 2SC/4-2 (11-12.4-fold resistant), and their 23- to 23.7-fold resistant 2SC/20-1 and 2SC/20-2 variants were isolated from highly tumorigenic (TrD(50) = 10 cells) and highly metastatic Rous sarcoma, virus-transformed Syrian hamster fibroblast HET-SR-2SC-LNM line for resistance to colchicine. 2SC/4 cells were less tumorigenic (TrD(50) = 70 cells) but as highly metastatic as parental counterparts. In contrast, both 2SC/20 variants showed a decrease in tumorigenicity (TrD(50) = 320 cells) and in the capability to produce spontaneous distant metastases. 2SC/20 cells almost lost the ability to colonize lungs in ex perimental metastasis assay. The autophosphorylation of pp60(src) tyrosine kinase in 2SC/20 cells was unaltered. The results suggest that i) selection of tumor cells for low levels of ''typical'' MDR leads to a decrease in the frequency of spontaneous and experimental metastases, and ii) alterations of malignancy in these cells are not caused by an impairment of function of a transforming oncogene.