Human pancreatic adenocarcinoma contains a side population resistant to gemcitabine

BMC Cancer

Research Article

Baki Topal¹  Anke Van den broeck²  Hugo Vankelecom³  Lies Gremeaux³ 

[1] Department of Abdominal Surgery, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium;Department of Abdominal Surgery, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium;Laboratory of Tissue Plasticity, Research Unit of Embryo and Stem Cells, Department of Development & Regeneration, University of Leuven (KU Leuven), Leuven, Belgium;Laboratory of Tissue Plasticity, Research Unit of Embryo and Stem Cells, Department of Development & Regeneration, University of Leuven (KU Leuven), Leuven, Belgium;

关键词: Pancreatic cancer;    Chemoresistance;    Side population;   

DOI  :  10.1186/1471-2407-12-354

 received in 2012-03-10, accepted in 2012-07-30,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTherapy 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(−like) phenotype.MethodsHuman 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.ResultsA 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.ConclusionWe 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

【 授权许可】

Unknown   
© Van den broeck et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.