Related Experiment Videos
Drug sensitivity and metastatic ability in B16 melanoma cells
Abstract:
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.
Insights
Metastatic ability in cancer cells does not necessarily correlate with resistance to chemotherapy. This study found that increased metastasis in B16 melanoma cells did not lead to parallel increases in resistance to N-phosphonacetyl-L-aspartate (PALA) or methotrexate (MTX).
Area of Science:
- Cancer Biology
- Pharmacology
- Tumor Metastasis
Background:
- Highly metastatic cancer cell lines often exhibit increased drug resistance.
- This observation suggests a potential parallel development of metastatic ability and drug resistance.
- The KHT fibrosarcoma and B16 melanoma models were previously used to study this phenomenon.
Purpose of the Study:
- To investigate whether increased metastatic potential in B16 melanoma cells is paralleled by altered resistance to chemotherapy.
- To determine if the selection for metastatic ability influences resistance to N-phosphonacetyl-L-aspartate (PALA) and methotrexate (MTX).
Main Methods:
- Serial passage of B16F1 melanoma cells as lung nodules (LP) to select for metastatic variants.
- Serial passage of B16F1 melanoma cells as leg tumors (LT) for comparison.
- Assessment of metastatic ability and drug resistance (PALA and MTX) at each passage.
Main Results:
- Serial lung passage (LP) significantly increased metastatic ability (100-fold) but did not increase PALA resistance; instead, MTX sensitivity increased.
- Serial leg tumor passage (LT) resulted in a modest increase in metastasis (3-fold) and MTX sensitivity, with a slight increase in PALA resistance.
- No instance showed a parallel increase in both metastatic ability and drug resistance.
Conclusions:
- The metastatic phenotype and drug resistance phenotype in B16 melanoma cells do not necessarily arise in parallel.
- Selection for increased metastasis does not consistently confer cross-resistance to PALA or MTX.
- These findings challenge the assumption of a shared underlying mechanism for metastasis and drug resistance in this model.