Comparative proteomic analysis of two stress-management strategies in pancreatic cancer

Abstract

Background: It is known that cancers adopt different strategies to cope with stress and overcome adverse micro-environmental conditions. Such strategies are also applicable to chemo-therapeutic treatment, which could subsequently result in chemo-resistance.

Materials and Methods: In order to investigate known stress-evasion strategies observed in pancreatic cancer, the stress-resistant KLM1-derived cell lines KLM1-R (Gemcitabine (GEM)- induced stress) and KLM1-S (growth factor restrictioninduced stress) were employed. Comparative proteomics were employed between for the two cell lines that were also compared against the parent cell line KLM1.

Results: Proteomic analysis revealed changes in the expression levels of 6 proteins, namely: transitional endoplasmic reticulum ATPase, lamin A/C, PDZ and LIM protein 1, calmodulin, heat shock protein 60 and alpha enolase. Resistance to GEM of KLM1-R and KLM1-S was found to be comparable, with KLM1-S cells exhibiting close to 1.5-fold higher halfmaximal inhibitory concentration (IC50) compared to KLM1- R cells.

Conclusion: These results suggest that KLM1-R can be used as a model of directly-acquired chemoresistance (responding directly to evade GEM treatment), while KLM1- S is a good model of indirectly-acquired chemoresistance (formed in response to having to survive with less availability of growth factors), additionally gaining a selective advantage upon GEM treatment.