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Title: Human pancreatic adenocarcinoma contains a side population resistant to gemcitabine
Authors: Van den Broeck, Anke
Gremeaux, Lies
Topal, Baki ×
Vankelecom, Hugo #
Issue Date: Aug-2012
Publisher: BioMed Central
Series Title: BMC Cancer vol:12
Article number: 354
Abstract: ABSTRACT: BACKGROUND: Therapy resistance remains one of the major challenges to improve the prognosis of patients with pancreatic cancer. Chemoresistant cells, which potentially also display cancer stem cell (CSC) characteristics, can be isolated using the side population (SP) technique. Our aim was to search for a SP in human pancreatic ductal adenocarcinoma (PDAC) and to examine its chemoresistance and CSC([MINUS SIGN]like) phenotype. METHODS: Human PDAC samples were expanded in immunodeficient mice and first-generation xenografts analyzed for the presence of a Hoechst dye-effluxing SP using flow cytometry (FACS). To investigate chemoresistance of the SP, mice bearing PDAC xenografts were treated with gemcitabine and SP proportion determined. In addition, the SP and the main tumour cell population (MP) were sorted by FACS for RNA extraction to profile gene expression, and for culturing under sphere-forming conditions. RESULTS: A SP was identified in all PDAC samples, analyzed. This SP was more resistant to gemcitabine than the other tumour cells as examined in vivo. Whole-genome expression profiling of the SP revealed upregulation of genes related to therapy resistance, apoptotic regulation and epithelial-mesenchymal transition. In addition, the SP displayed higher tumourigenic (CSC) activity than the MP as analyzed in vitro by sphere-forming capacity. CONCLUSION: We identified a SP in human PDAC and uncovered a chemoresistant and CSC-associated phenotype. This SP may represent a new therapeutic target in pancreatic cancer.Trial registrationClinicaltrials.gov NCT00936104.
URI: 
ISSN: 1471-2407
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Abdominal Surgical Oncology
Embryo and Stemcells (-)
× corresponding author
# (joint) last author

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