期刊
CANCER SCIENCE
卷 106, 期 9, 页码 1182-1187出版社
WILEY-BLACKWELL
DOI: 10.1111/cas.12734
关键词
Cancer stem cell; cancer therapy; induced pluripotent stem cell; pancreatic cancer; reprogramming
类别
资金
- Taiho Pharmaceutical Co., Ltd.
- Evidence Based Medical (EBM) Research Center Yakult Honsha Co., Ltd.
- Chugai Co., Ltd.
- Merck Co., Ltd.
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.
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