The expression of P-glycoprotein is causally related to a less aggressive phenotype in human osteosarcoma cells

The relationship between P-glycoprotein expression and malignancy is contro versial. We have recently found that, in osteosarcoma, multidrug resistance (MDR) is associated with a less aggressive behavior, both in vitro and in clinical settings. In this study, we evaluated whether P-glycoprotein overe xpression has a cause-effect relationship with the reduced metastatic poten tial of MDR cells, or rather reflects a more complex phenotype, MDR1 gene-t ransfected osteosarcoma cell clones, showing different levels of P-glycopro tein expression, were analysed for their in vitro characteristics and their tumorigenic and metastatic ability in athymic mice. Apart from the differe nt levels of P-glycoprotein, no significant change in the expression of sur face antigens or in the differentiative features were observed in the MDR1 gene transfectants compared to the parental cell lines or control clones, o btained by transfection with neo gene alone. In contrast to controls, howev er, MDR1 transfectants showed a significantly lower ability to grow in semi -solid medium and were completely unable to grow and give lung metastases i n athymic mice. These findings indicate that P-glycoprotein overexpression is causally associated with a low malignant potential of osteosarcoma cells , and open new insights on the role and functions of P-glycoprotein activit y.