DNA methylation in the tumor microenvironment

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 tumorassociated stromal components including fibroblasts and immune cells. We also discuss the potential for targeting DNA methylation for the treatment of cancers.

摘 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。