MUC4 down-regulation reverses chemoresistance of pancreatic cancer stem/progenitor cells and their progenies

Murielle Mimeault; Sonny L. Johansson; Shantibhusan Senapati; Navneet Momi; Subhankar Chakraborty; Surinder K. Batra

doi:10.1016/j.canlet.2010.02.015

MUC4 down-regulation reverses chemoresistance of pancreatic cancer stem/progenitor cells and their progenies

Murielle Mimeault, Sonny L. Johansson, Shantibhusan Senapati, Navneet Momi, Subhankar Chakraborty, Surinder K. Batra

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

Abstract

The present study was undertaken to estimate the therapeutic benefit to down-regulate the MUC4 mucin for reversing chemoresistance of pancreatic cancer (PC) stem/progenitor cells and their progenies. The results have revealed that MUC4 mucin is overexpressed in CD133⁺ and CD133^- pancreatic cells (PCs) detected in patient's adenocarcinoma tissues while no significant expression was seen in normal pancreatic tissues. The gain- and loss-of-function analyses have indicated that the overexpression of MUC4 in PC lines is associated with a higher resistance to the anti-proliferative, anti-invasive and apoptotic effects induced by gemcitabine. Importantly, the treatment of the MUC4-overexpressing CD18/HPAF-Src cells with gemcitabine resulted in an enrichment of the side population (SP) cells expressing CD133 while the total PC cells including non-SP cells detected in MUC4 knockdown CD18/HPAF-shMUC4 cells were responsive to the cytotoxic effects induced by gemcitabine. These data suggest that the MUC4 down-regulation may constitute a potential therapeutic strategy for improving the efficacy of gemcitabine to eradicate the total PC cell mass, and thereby preventing disease relapse.

Original language	English (US)
Pages (from-to)	69-84
Number of pages	16
Journal	Cancer Letters
Volume	295
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2010.02.015
State	Published - Sep 2010

Keywords

Cancer therapies
Chemoresistance
Gemcitabine
MUC4 mucin
Pancreatic cancer
Pancreatic stem/progenitor cells
Side population

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2010.02.015

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title = "MUC4 down-regulation reverses chemoresistance of pancreatic cancer stem/progenitor cells and their progenies",

abstract = "The present study was undertaken to estimate the therapeutic benefit to down-regulate the MUC4 mucin for reversing chemoresistance of pancreatic cancer (PC) stem/progenitor cells and their progenies. The results have revealed that MUC4 mucin is overexpressed in CD133+ and CD133- pancreatic cells (PCs) detected in patient's adenocarcinoma tissues while no significant expression was seen in normal pancreatic tissues. The gain- and loss-of-function analyses have indicated that the overexpression of MUC4 in PC lines is associated with a higher resistance to the anti-proliferative, anti-invasive and apoptotic effects induced by gemcitabine. Importantly, the treatment of the MUC4-overexpressing CD18/HPAF-Src cells with gemcitabine resulted in an enrichment of the side population (SP) cells expressing CD133 while the total PC cells including non-SP cells detected in MUC4 knockdown CD18/HPAF-shMUC4 cells were responsive to the cytotoxic effects induced by gemcitabine. These data suggest that the MUC4 down-regulation may constitute a potential therapeutic strategy for improving the efficacy of gemcitabine to eradicate the total PC cell mass, and thereby preventing disease relapse.",

keywords = "Cancer therapies, Chemoresistance, Gemcitabine, MUC4 mucin, Pancreatic cancer, Pancreatic stem/progenitor cells, Side population",

author = "Murielle Mimeault and Johansson, {Sonny L.} and Shantibhusan Senapati and Navneet Momi and Subhankar Chakraborty and Batra, {Surinder K.}",

note = "Funding Information: The authors on this work are supported by grants from the National Institutes of Health (CA78590, CA111294 , CA133774 and CA131944 ). ",

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language = "English (US)",

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AU - Mimeault, Murielle

AU - Johansson, Sonny L.

AU - Senapati, Shantibhusan

AU - Momi, Navneet

AU - Chakraborty, Subhankar

AU - Batra, Surinder K.

N1 - Funding Information: The authors on this work are supported by grants from the National Institutes of Health (CA78590, CA111294 , CA133774 and CA131944 ).

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AB - The present study was undertaken to estimate the therapeutic benefit to down-regulate the MUC4 mucin for reversing chemoresistance of pancreatic cancer (PC) stem/progenitor cells and their progenies. The results have revealed that MUC4 mucin is overexpressed in CD133+ and CD133- pancreatic cells (PCs) detected in patient's adenocarcinoma tissues while no significant expression was seen in normal pancreatic tissues. The gain- and loss-of-function analyses have indicated that the overexpression of MUC4 in PC lines is associated with a higher resistance to the anti-proliferative, anti-invasive and apoptotic effects induced by gemcitabine. Importantly, the treatment of the MUC4-overexpressing CD18/HPAF-Src cells with gemcitabine resulted in an enrichment of the side population (SP) cells expressing CD133 while the total PC cells including non-SP cells detected in MUC4 knockdown CD18/HPAF-shMUC4 cells were responsive to the cytotoxic effects induced by gemcitabine. These data suggest that the MUC4 down-regulation may constitute a potential therapeutic strategy for improving the efficacy of gemcitabine to eradicate the total PC cell mass, and thereby preventing disease relapse.

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KW - Pancreatic cancer

KW - Pancreatic stem/progenitor cells

KW - Side population

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MUC4 down-regulation reverses chemoresistance of pancreatic cancer stem/progenitor cells and their progenies

Abstract

Keywords

ASJC Scopus subject areas

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