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 (TrD50 = 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 (TrD50 = 70 cells) but as highly metastatic as parental counterparts. In contrast, both 2SC/20 variants showed a decrease in tumorigenicity (TrD50 = 320 cells) and in the capability to produce spontaneous distant metastases. 2SC/20 cells almost lost the ability to colonize lungs in experimental metastasis assay. The autophosphorylation of pp60src 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.
Shtil
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A
Laboratory of Tumor Cell Genetics, Institute of Carcinogenesis, Cancer Research Center, Moscow, Russia.
Shushanov
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A
Moynova
E
E
Stavrovskaya
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000818:Animals; D001358:Avian Sarcoma Viruses; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D006224:Cricetinae; D018432:Drug Resistance, Multiple / Q000502:physiology*; D008297:Male; D008647:Mesocricetus; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000032:analysis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins; D016392:Proto-Oncogene Proteins pp60(c-src)