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Characterization of MBT-2 tumour cell "variant" resistant to tumour necrosis factor
S A Kadhim1, J Y Wang, B McLean
1Department of Surgery, University Hospital, University of Western Ontario, London, Canada.
Abstract:
Previously we reported sensitivity of MBT-2 murine bladder tumour to tumour necrosis factor (TNF) in vivo and in vitro [8]. We showed that with prolonged exposure of cultured MBT-2 tumour cells to TNF, a resistant MBT-2 "variant" tumour cell population emerged in vitro. This concurred with the finding of transient in vivo cytotoxic effect of TNF against MBT-2 tumour. Herein, we delineate phenotypic changes in MBT-2 cells associated with TNF resistance. Parent MBT-2 (MBT-2P) and the TNF-resistant "variant" MBT-2R cells were compared in terms of in vitro sensitivity to TNF, DNA profile, karyotype and in vitro growth kinetics. We conclude that acquisition of resistance to TNF may be due to cell cycle derangement and differences in in vitro growth characteristics. DNA indices and karyotype of "variant" MBT-2R cells were not altered, indicating the anti-tumour action of TNF is not-mutagenic.
Insights
Tumor necrosis factor (TNF) resistance in MBT-2 bladder cancer cells emerged after prolonged exposure. This resistance is linked to cell cycle changes, not genetic mutations, suggesting TNF
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Previously, MBT-2 murine bladder tumors demonstrated sensitivity to tumor necrosis factor (TNF).
- Prolonged in vitro exposure to TNF led to the emergence of a TNF-resistant MBT-2 variant cell population.
- This in vitro observation correlated with the transient in vivo cytotoxic effect of TNF against MBT-2 tumors.
Purpose of the Study:
- To delineate the phenotypic changes in MBT-2 cells associated with acquired TNF resistance.
- To compare parent MBT-2 (MBT-2P) and TNF-resistant MBT-2R cells regarding TNF sensitivity, DNA profile, karyotype, and growth kinetics.
Main Methods:
- In vitro sensitivity assays to TNF.
- DNA profiling and karyotyping of parent and variant cells.
- Assessment of in vitro growth kinetics.
Main Results:
- Phenotypic characterization of MBT-2 cells revealed differences associated with TNF resistance.
- Comparison between MBT-2P and MBT-2R cells highlighted variations in TNF sensitivity and growth characteristics.
- DNA indices and karyotypes of MBT-2R cells remained unaltered compared to MBT-2P cells.
Conclusions:
- Acquisition of TNF resistance in MBT-2 cells may be attributed to cell cycle derangements and altered in vitro growth characteristics.
- The anti-tumor action of TNF is not mutagenic, as evidenced by the stable DNA indices and karyotypes in resistant cells.
- Understanding these mechanisms is crucial for optimizing TNF-based cancer therapies.