Isolation of a growth factor stress-induced pancreatic cancer sub-population: insight into changes due to micro-environment.

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.

• Authors: Byron Baron, Takao Kitagawa, Kazuyuki Nakamura, Yasuhiro Kuramitsu
• Journal: Cancer genomics & proteomics (Cancer Genomics Proteomics) 2015 Mar-Apr Vol. 12 Issue 2 Pg. 49-55 ISSN: 1790-6245 [Electronic] Greece
• PMID: 25770187 (Publication Type: Journal Article)
• Copyright: Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Intercellular Signaling Peptides and Proteins
• Neoplasm Proteins

Topics

• Biological Assay
• Blotting, Western
• Cell Line, Tumor
• Cell Separation
• Cell Shape (drug effects)
• Cell Survival (drug effects)
• Electrophoresis, Gel, Two-Dimensional
• Endoplasmic Reticulum Chaperone BiP
• Humans
• Intercellular Signaling Peptides and Proteins (pharmacology)
• Mass Spectrometry
• Neoplasm Proteins (metabolism)
• Pancreatic Neoplasms (pathology)
• Proteomics
• Stress, Physiological (drug effects)
• Tumor Microenvironment (drug effects)
• Wound Healing (drug effects)