Susceptibility of pancreatic cancer stem cells to reprogramming

Cancer Science

Kozo Noguchi³  Hidetoshi Eguchi³  Masamitsu Konno¹  Koichi Kawamoto³  Naohiro Nishida¹  Jun Koseki²  Hiroshi Wada³  Shigeru Marubashi³  Hiroaki Nagano³  Yuichiro Doki³  Masaki Mori³ 

[1] Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan;Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Osaka, Japan;Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

关键词: Cancer stem cell;    cancer therapy;    induced pluripotent stem cell;    pancreatic cancer;    reprogramming;   

DOI  :  10.1111/cas.12734

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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