Isolation of a Growth Factor Stress-induced Pancreatic Cancer Sub-population: Insight into Changes Due to Micro-environment

摘要

Background: Micro-environment plays a crucial role in determining the phenotypes within a tumor. Materials and Methods: In order to understand how the micro-environment affects pancreatic cancer, KLM1 cells were cultured under growth factor stress by culturing in foetal bovine serum (FBS)-free and reduced (1%) medium over several passages to mimic the core of a solid tumor with low vascularisation. Results: Proteomic analysis on these conditioned pancreatic cancer cells, called KLM1-S, compared to the parent cell line KLM1 revealed that a number of proteins including ?±-enolase, GAPDH, GRP78, HSP60 and STIP-1 were dysregulated. Additionally, KLM1-S cells exhibited a 250-fold increase in half-maximal inhibitory concentration (IC50) over the parent cell line KLM1. Conclusion: By decreasing their replication rate and levels of intracellular reactive oxygen species (ROS), KLM1-S cells are able to resist gemcitabine (GEM). The results obtained suggest that in KLM1 different phenotypes are a result of cellular plasticity rather than a committed transformation.