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CLC number: R730.231

On-line Access: 2017-05-04

Received: 2016-12-19

Revision Accepted: 2017-02-12

Crosschecked: 2017-04-19

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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.5 P.365-372

10.1631/jzus.B1600579


DNA methylation in the tumor microenvironment


Author(s):  Meng-wen Zhang, Kenji Fujiwara, Xu Che, Shu Zheng, Lei Zheng

Affiliation(s):  The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; more

Corresponding email(s):   zhengshu@zju.edu.cn, lzheng6@jhmi.edu

Key Words:  Tumor microenvironment (TME), DNA methylation, Cancer-associated fibroblasts, Cancer-associated immune cells, Epigenetic therapy


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Meng-wen Zhang, Kenji Fujiwara, Xu Che, Shu Zheng, Lei Zheng. DNA methylation in the tumor microenvironment[J]. Journal of Zhejiang University Science B, 2017, 18(1): 365-372.

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author="Meng-wen Zhang, Kenji Fujiwara, Xu Che, Shu Zheng, Lei Zheng",
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pages="365-372",
year="2017",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600579"
}

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T1 - DNA methylation in the tumor microenvironment
A1 - Meng-wen Zhang
A1 - Kenji Fujiwara
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Abstract: 
The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells can induce DNA methylation in cancer-associated fibroblasts (CAFs), thereby modifying tumor-stromal interactions in the TME, and subsequently creating a TME that supports tumor growth. Here we summarize recent studies about how DNA methylation affects tumorigenesis through regulating tumor-associated stromal components including fibroblasts and immune cells. We also discuss the potential for targeting DNA methylation for the treatment of cancers.

肿瘤微环境中的甲基化调节机制

概要:肿瘤微环境主要由肿瘤细胞、肿瘤相关间质细胞及细胞外基质组成。肿瘤细胞通过多种方式调控肿瘤微环境中的间质细胞,诱导间质细胞分化并发挥促肿瘤的作用,从而为肿瘤的生长及转移创造一个适宜的环境。DNA甲基化异常是肿瘤的特点。目前关于肿瘤的甲基化调控机制已有大量报道,对于肿瘤细胞与微环境中间质细胞的相互作用机制也有了一些报道。然而,关于肿瘤细胞对微环境间质细胞的甲基化调控机制以及这种调控对肿瘤发生发展的影响并没有系统的论述。本综述总结了肿瘤细胞对微环境中间质细胞甲基化调控机制的最新研究进展,以及间质细胞发生的一些促肿瘤改变,从而全面阐释了肿瘤细胞和间质细胞间的相互作用,同时总结了肿瘤细胞对肿瘤微环境的表观遗传学调控,尤其是甲基化调控在肿瘤进展中发挥了重要的作用。干预肿瘤细胞对微环境中间质细胞的甲基化调节过程,可以发挥抗肿瘤的作用。
关键词:肿瘤微环境;DNA甲基化;肿瘤相关成纤维细胞;肿瘤相关免疫细胞;表观遗传学治疗

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