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

被引:13
作者
SHTIL, A [1 ]
SHUSHANOV, A [1 ]
MOYNOVA, E [1 ]
STAVROVSKAYA, A [1 ]
机构
[1] CANC RES CTR,INST CARCINOGENESIS,REGULAT VIRAL & CELLULAR ONCOGENES LAB,MOSCOW,RUSSIA
关键词
METASTASIS; RESISTANCE; MULTIDRUG; MULTIDRUG RESISTANCE;
D O I
10.1016/S0940-2993(11)80096-5
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:257 / 262
页数:6
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