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 journalArticle

52 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 languageEnglish (US)
Pages (from-to)69-84
Number of pages16
JournalCancer Letters
Volume295
Issue number1
DOIs
StatePublished - 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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