Abstract

Background: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.Methods:Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.Results:A subpopulation of cells displayed PD2 overexpression in mouse (Kras G12D; Pdx1-Cre and Kras G12D; Trp53 R172H/+; Pdx1-Cre) and human pancreatic tumours, which co-express CSC markers. Cancer stem cells exhibited elevated expression of PD2 and self-renewal markers, such as Oct3/4, Shh and β-catenin. Gemcitabine treatment maintained the CSC population with simultaneous maintenance of PD2 and CSC marker expression. Knockdown of PD2 in CSCs resulted in reduced viability of cells and enhanced apoptosis along with abrogated expression of CD133 and MDR2.Conclusions:Our results suggest that PD2 is a novel CSC maintenance protein, loss of which renders the CSCs more susceptible to drug-induced cell death.

Original languageEnglish (US)
Pages (from-to)486-496
Number of pages11
JournalBritish journal of cancer
Volume111
Issue number3
DOIs
StatePublished - Jul 29 2014

Fingerprint

Neoplastic Stem Cells
Pancreatic Neoplasms
Drug Resistance
gemcitabine
Maintenance
Apoptosis
Catenins
Disease Resistance
Gene Targeting
Cell Survival
Cell Death
Stem Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{97a03d50471a4d7a9721248a7213b870,
title = "Novel role of pancreatic differentiation 2 in facilitating self-renewal and drug resistance of pancreatic cancer stem cells",
abstract = "Background: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.Methods:Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.Results:A subpopulation of cells displayed PD2 overexpression in mouse (Kras G12D; Pdx1-Cre and Kras G12D; Trp53 R172H/+; Pdx1-Cre) and human pancreatic tumours, which co-express CSC markers. Cancer stem cells exhibited elevated expression of PD2 and self-renewal markers, such as Oct3/4, Shh and β-catenin. Gemcitabine treatment maintained the CSC population with simultaneous maintenance of PD2 and CSC marker expression. Knockdown of PD2 in CSCs resulted in reduced viability of cells and enhanced apoptosis along with abrogated expression of CD133 and MDR2.Conclusions:Our results suggest that PD2 is a novel CSC maintenance protein, loss of which renders the CSCs more susceptible to drug-induced cell death.",
author = "Vaz, {A. P.} and {Palanimuthu Ponnusamy}, Moorthy and Satyanarayana Rachagani and P. Dey and Ganti, {Apar Kishor P} and Batra, {Surinder Kumar}",
year = "2014",
month = "7",
day = "29",
doi = "10.1038/bjc.2014.152",
language = "English (US)",
volume = "111",
pages = "486--496",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Novel role of pancreatic differentiation 2 in facilitating self-renewal and drug resistance of pancreatic cancer stem cells

AU - Vaz, A. P.

AU - Palanimuthu Ponnusamy, Moorthy

AU - Rachagani, Satyanarayana

AU - Dey, P.

AU - Ganti, Apar Kishor P

AU - Batra, Surinder Kumar

PY - 2014/7/29

Y1 - 2014/7/29

N2 - Background: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.Methods:Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.Results:A subpopulation of cells displayed PD2 overexpression in mouse (Kras G12D; Pdx1-Cre and Kras G12D; Trp53 R172H/+; Pdx1-Cre) and human pancreatic tumours, which co-express CSC markers. Cancer stem cells exhibited elevated expression of PD2 and self-renewal markers, such as Oct3/4, Shh and β-catenin. Gemcitabine treatment maintained the CSC population with simultaneous maintenance of PD2 and CSC marker expression. Knockdown of PD2 in CSCs resulted in reduced viability of cells and enhanced apoptosis along with abrogated expression of CD133 and MDR2.Conclusions:Our results suggest that PD2 is a novel CSC maintenance protein, loss of which renders the CSCs more susceptible to drug-induced cell death.

AB - Background: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.Methods:Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.Results:A subpopulation of cells displayed PD2 overexpression in mouse (Kras G12D; Pdx1-Cre and Kras G12D; Trp53 R172H/+; Pdx1-Cre) and human pancreatic tumours, which co-express CSC markers. Cancer stem cells exhibited elevated expression of PD2 and self-renewal markers, such as Oct3/4, Shh and β-catenin. Gemcitabine treatment maintained the CSC population with simultaneous maintenance of PD2 and CSC marker expression. Knockdown of PD2 in CSCs resulted in reduced viability of cells and enhanced apoptosis along with abrogated expression of CD133 and MDR2.Conclusions:Our results suggest that PD2 is a novel CSC maintenance protein, loss of which renders the CSCs more susceptible to drug-induced cell death.

UR - http://www.scopus.com/inward/record.url?scp=84905220359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905220359&partnerID=8YFLogxK

U2 - 10.1038/bjc.2014.152

DO - 10.1038/bjc.2014.152

M3 - Article

C2 - 25003666

AN - SCOPUS:84905220359

VL - 111

SP - 486

EP - 496

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 3

ER -