Drug sensitivity and metastatic ability in B16 melanoma cells.

We have previously reported that highly metastatic cell lines derived from KHT fibrosarcoma (KHT 35L1) and B16 melanoma (B16F10) are more resistant to N-phosphonacetyl-L-aspartate (PALA) and methotrexate (MTX) than the parental cell lines. This correlation between drug resistance and metastatic ability suggested the possibility that both phenotypes might have arisen in parallel as a result of a similar mechanism. In this study, we examined this possibility by reproducing the selection procedure for B16F10 cells (by serial passage of B16F1 cells as lung nodules) and testing the cells at each passage for changes in resistance to PALA and MTX. The results confirm that serial passage of B16F1 cells as lung nodules (LP) selects for cells with increasing metastatic ability (100-fold after seven passages), but these cells did not develop increased resistance to PALA and became more sensitive to MTX. For comparison B16F1 cells were also serially passaged (six passages) as leg tumors (LT). These cells became slightly more metastatic (3-fold) than B16F1 cells maintained in tissue culture, and demonstrated a small increase in sensitivity to MTX, as in the LP lines. There was also an apparent increase in resistance to PALA. In no instance was there a parallel increase in drug resistance and metastatic ability indicating that these two phenotypes do not necessarily arise in parallel in this cell line.