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Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes

In many types of cancers, a side population (SP) has been identified based on high efflux capacity, thereby enriching for chemoresistant cells as well as for candidate cancer stem cells (CSC). Here, we explored whether human pancreatic ductal adenocarcinoma (PDAC) contains a SP, and whether its gene...

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Autores principales: Van den broeck, Anke, Vankelecom, Hugo, Van Delm, Wouter, Gremeaux, Lies, Wouters, Jasper, Allemeersch, Joke, Govaere, Olivier, Roskams, Tania, Topal, Baki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775803/
https://www.ncbi.nlm.nih.gov/pubmed/24069258
http://dx.doi.org/10.1371/journal.pone.0073968
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author Van den broeck, Anke
Vankelecom, Hugo
Van Delm, Wouter
Gremeaux, Lies
Wouters, Jasper
Allemeersch, Joke
Govaere, Olivier
Roskams, Tania
Topal, Baki
author_facet Van den broeck, Anke
Vankelecom, Hugo
Van Delm, Wouter
Gremeaux, Lies
Wouters, Jasper
Allemeersch, Joke
Govaere, Olivier
Roskams, Tania
Topal, Baki
author_sort Van den broeck, Anke
collection PubMed
description In many types of cancers, a side population (SP) has been identified based on high efflux capacity, thereby enriching for chemoresistant cells as well as for candidate cancer stem cells (CSC). Here, we explored whether human pancreatic ductal adenocarcinoma (PDAC) contains a SP, and whether its gene expression profile is associated with chemoresistance, CSC and prognosis. After dispersion into single cells and incubation with Hoechst dye, we analyzed human PDAC resections specimens using flow cytometry (FACS). We identified a SP and main population (MP) in all human PDAC resection specimens (n = 52) analyzed, but detected immune (CD45(+)) and endothelial (CD31(+)) cells in this fraction together with tumor cells. The SP and MP cells, or more purified fractions depleted from CD31(+)/CD45(+) cells (pSP and pMP), were sorted by FACS and subjected to whole-genome expression analysis. This revealed upregulation of genes associated with therapy resistance and of markers identified before in putative pancreatic CSC. pSP gene signatures of 32 or 10 up- or downregulated genes were developed and tested for discriminatory competence between pSP and pMP in different sets of PDAC samples. The prognostic value of the pSP genes was validated in a large independent series of PDAC patients (n = 78) using nCounter analysis of expression (in tumor versus surrounding pancreatic tissue) and Cox regression for disease-free and overall survival. Of these genes, expression levels of ABCB1 and CXCR4 were correlated with worse patient survival. Thus, our study for the first time demonstrates that human PDAC contains a SP. This tumor subpopulation may represent a valuable therapeutic target given its chemoresistance- and CSC-associated gene expression characteristics with potential prognostic value.
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spelling pubmed-37758032013-09-25 Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes Van den broeck, Anke Vankelecom, Hugo Van Delm, Wouter Gremeaux, Lies Wouters, Jasper Allemeersch, Joke Govaere, Olivier Roskams, Tania Topal, Baki PLoS One Research Article In many types of cancers, a side population (SP) has been identified based on high efflux capacity, thereby enriching for chemoresistant cells as well as for candidate cancer stem cells (CSC). Here, we explored whether human pancreatic ductal adenocarcinoma (PDAC) contains a SP, and whether its gene expression profile is associated with chemoresistance, CSC and prognosis. After dispersion into single cells and incubation with Hoechst dye, we analyzed human PDAC resections specimens using flow cytometry (FACS). We identified a SP and main population (MP) in all human PDAC resection specimens (n = 52) analyzed, but detected immune (CD45(+)) and endothelial (CD31(+)) cells in this fraction together with tumor cells. The SP and MP cells, or more purified fractions depleted from CD31(+)/CD45(+) cells (pSP and pMP), were sorted by FACS and subjected to whole-genome expression analysis. This revealed upregulation of genes associated with therapy resistance and of markers identified before in putative pancreatic CSC. pSP gene signatures of 32 or 10 up- or downregulated genes were developed and tested for discriminatory competence between pSP and pMP in different sets of PDAC samples. The prognostic value of the pSP genes was validated in a large independent series of PDAC patients (n = 78) using nCounter analysis of expression (in tumor versus surrounding pancreatic tissue) and Cox regression for disease-free and overall survival. Of these genes, expression levels of ABCB1 and CXCR4 were correlated with worse patient survival. Thus, our study for the first time demonstrates that human PDAC contains a SP. This tumor subpopulation may represent a valuable therapeutic target given its chemoresistance- and CSC-associated gene expression characteristics with potential prognostic value. Public Library of Science 2013-09-17 /pmc/articles/PMC3775803/ /pubmed/24069258 http://dx.doi.org/10.1371/journal.pone.0073968 Text en © 2013 Van den broeck et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Van den broeck, Anke
Vankelecom, Hugo
Van Delm, Wouter
Gremeaux, Lies
Wouters, Jasper
Allemeersch, Joke
Govaere, Olivier
Roskams, Tania
Topal, Baki
Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes
title Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes
title_full Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes
title_fullStr Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes
title_full_unstemmed Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes
title_short Human Pancreatic Cancer Contains a Side Population Expressing Cancer Stem Cell-Associated and Prognostic Genes
title_sort human pancreatic cancer contains a side population expressing cancer stem cell-associated and prognostic genes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775803/
https://www.ncbi.nlm.nih.gov/pubmed/24069258
http://dx.doi.org/10.1371/journal.pone.0073968
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