癌相关成纤维细胞表型转换的遗传学与表观遗传学机制研究现状

Advancement of Phenotype Transformation of Cancer-associated Fibroblasts: from Genetic Alterations to Epigenetic Modification

在肿瘤基础研究中,近年来对作为"土壤"的肿瘤微环境的探索逐渐增多。作为肿瘤微环境的主要成分,癌相关成纤维细胞(cancer-associated fibroblasts,CAFs)在肿瘤发生、进展及预后中的作用被逐步阐明。而CAFs表型形成机制的阐明将有助于更深刻的理解其在肿瘤中的作用。CAFs主要有四种起源:上皮细胞、内皮细胞、间质干细胞和局部的间质细胞。研究发现,不同起源的CAFs具有大致相同的表型特征,而CAFs表型转换的机制却不甚清楚。目前的研究主要集中在:1CAFs基因的改变;2CAFs表观遗传学改变。本文将在阐述CAFs起源多样性和表型特征一致性的基础上,系统总结CAFs表型转换的表观遗传学机制的现状和最新进展。

In the ifeld of human cancer research, even though the vast majority attentions were paid to tumor cells as“the seeds”, the roles of tumor microenvironments as“the soil”are gradually explored in recent years. As a dominant com-partment of tumor microenvironments, cancer-associated ifbroblasts （CAFs） were discovered to correlated with tumorigenesis, tumor progression and prognosis. And the exploration of the mechanisms of CAF phenotype transformation would conducive to the further understand of the CAFs function in human cancers. As we known that CAFs have four main origins, including epithelial cells, endothelial cells, mesenchymal stem cells （MSCs） and local mesenchymal cells. However, researchers found that all these origins ifnally conduct similiar phenotypes from intrinsic to extrinsic ones. hTus, what and how a mechanism can conduct the phenotype transformation of CAFs with different origins？ Two viewpoints are proposed to try to answer the quet-sion, involving genetic alterations and epigenetic modiifcations. hTis review will systematically summarize the advancement of mechanisms of CAF phenotype transformations in the aspect of genentic and epigenetic modiifcations.