Susceptibility of pancreatic cancer stem cells to reprogramming

Kozo Noguchi, Hidetoshi Eguchi, Masamitsu Konno, Koichi Kawamoto, Naohiro Nishida, Jun Koseki, Hiroshi Wada, Shigeru Marubashi, Hiroaki Nagano, Yuichiro Doki, Masaki Mori, Hideshi Ishii

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Previous reports have indicated that reprogramming technologies may be useful for altering the malignant phenotype of cancer cells. Although somatic stem cells in normal tissues are more sensitive to reprogramming induction than differentiated cells, it remains to be elucidated whether any specific subpopulations are sensitive to reprogramming in heterogeneous tumor tissues. Here we examined the susceptibility of pancreatic cancer stem cells (CSC) and non-CSC to reprogramming. To characterize CSC populations, we focused on c-Met signaling, which has been identified as a marker of CSC in mouse experiments in vivo. Cells that expressed high levels of c-Met showed higher CSC properties, such as tumor-initiating capacity, and resistance to gemcitabine. Real-time reverse transcription-polymerase chain reaction in cells expressing high levels of c-Met revealed endogenous expression of reprogramming factors, such as OCT3/4, SOX2, KLF4 and cMYC. Introduction of these four factors resulted in higher alkaline phosphatase staining in cells with high c-Met expression than in controls. Therefore, the study results demonstrate that cellular reprogramming may be useful for extensive epigenetic modification of malignant features of pancreatic CSC.

Original languageEnglish
Pages (from-to)1182-1187
Number of pages6
JournalCancer Science
Volume106
Issue number9
DOIs
Publication statusPublished - Sep 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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