Susceptibility of pancreatic cancer stem cells to reprogramming.
Susceptibility of pancreatic cancer stem cells to reprogramming.
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DOI：
10.1111/cas.12734
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发表时间：
2015-09
期刊：
影响因子：
5.7
通讯作者：
Ishii H
中科院分区：
文献类型：
--
作者：
Noguchi K;Eguchi H;Konno M;Kawamoto K;Nishida N;Koseki J;Wada H;Marubashi S;Nagano H;Doki Y;Mori M;Ishii H
先前的报道表明，重编程技术可能有助于改变癌细胞的恶性表型。尽管正常组织中的体细胞干细胞比分化细胞对重编程诱导更敏感，但在异质肿瘤组织中是否有特定的亚群对重编程敏感仍有待阐明。本文研究了胰腺癌干细胞（CSC）和非CSC对重编程的易感性。为了表征CSC群体，我们重点研究了c-Met信号，该信号已在小鼠体内实验中被确定为CSC的标志物。表达高水平c-Met的细胞显示出更高的CSC特性，如肿瘤启动能力和对吉西他滨的抗性。在高水平c-Met表达的细胞中，实时逆转录聚合酶链反应揭示了内源性重编程因子，如OCT3/4、SOX2、KLF4和cMYC的表达。这四个因素的引入导致高c-Met表达的细胞碱性磷酸酶染色高于对照组。因此，研究结果表明，细胞重编程可能有助于胰腺CSC恶性特征的广泛表观遗传修饰。
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.