The effects of gossypol on the invasiveness of MAT-LyLu cells and MAT-LyLu cells from the metastasized lungs of MAT-LyLu-bearing Copenhagen rats.

Recently, we isolated a novel subline of the MAT-LyLu cell line from the metastasized lungs of MAT-LyLu-bearing Copenhagen rats (MLL cells). In this study, we compared the MLL cells to the parental MAT-LyLu cells with respect to invasive ability, mRNA expression level for the nm23 metastasis suppressor gene, and response to gossypol (GP), a natural compound with documented antiproliferative and antimetastatic activity, in an in vitro invasion assay. ML cells were isolated from mechanically dissociated metastasized lungs from MAT-LuLu-bearing Copenhagen rats. Comparisons of the invasive ability and steady-state levels of nm23 mRNA between MLL and MAT-LuLu cells were determined by in vitro invasion assay and RT-PCR, respectively. The results show that MLL cells display a higher penetration percentage than MAT-LyLu cells in the in vitro invasion assay. Furthermore, RT-PCR revealed that MLL cells possess lower steady state levels of nm23 mRNA than MAT-LyLu cells, suggesting a molecular basis for the observed differences in in vitro invasive ability. Finally, both MLL and MAT-LyLu cells were susceptible to gossypol, which induced dose-dependent inhibition of invasive activity. These results report the isolation of a novel, more highly invasive subline of the MAT-LyLu cell line that is as susceptible to the inhibitory effects of gossypol as the parental MAT-LyLu cells. The MLL cells, in combination with the parental MAT-LyLu cells, can be valuable tools for investigating the biology and behavior of metastatic cells and their response to chemotherapeutic/preventive agents.