Byron Baron1, Takao Kitagawa2, Kazuyuki Nakamura3, Yasuhiro Kuramitsu2. 1. Department of Anatomy and Cell Biology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi, Japan. 2. Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi, Japan. 3. Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi, Japan Centre of Clinical Laboratories in Tokuyama Medical Association Hospital, Shunan-shi, Japan.
Abstract
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 α-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. Copyright
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 α-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. Copyright