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We studied whether acquisition of multidrug resistance (MDR) by tumor cells can alter their integrin profile and malignant behavior. Hamster fibroblast cell line HET-SR-2SC-LNM was selected for MDR, yielding the 2SC/20 subline. Compared with the parental cells, the 2SC/20 subline weakly adhered to denatured collagen (dCol) which correlated with decreased expression of alphavbeta3, a dCol receptor. Importantly, 2SC/20 subline demonstrated significantly decreased activity of collagenase MMP-2, lower ability to invade Matrigel, and attenuated metastasis in syngeneic animals. We provide evidence for the first time that selection for MDR can be associated with down-regulation of alphavbeta3 integrin, supporting our recent proof of the pro-apoptotic role of this integrin (Oncogene 20 (2001) 4710). Lack of alphavbeta3 expression may link cell survival under toxic conditions with decreased malignancy of the resulting drug resistant tumor.

Thymidine transport was found to be increased two-fold at a permissive temperature in the cells of a normal rat kidney (NRK) line which was infected with a temperature-sensitive Rous sarcoma virus. This increase in thymidine transport was independent of cell density and coincided with the changes in cellular morphology that result from this temperature shift. A double reciprocal plot of the data demonstrated two saturable components (Km values of 60 microM and 250 microM at 39 degrees, non-permissive temperature) of the uptake of thymidine, and the drop of temperature (at 33 degrees, the permissive temperature for transformation) decreased Km to one half, but did not change Vmax. These results indicate that a qualitative alteration of thymidine transport took place in the presence of the active src gene product.