作用虽小,影响重大:微小RNA作为癌症相关成纤维细胞与癌细胞间相互作用的沟通者

Small role with big impact: miRNAs as communicators in the cross-talk between cancer-associated fibroblasts and cancer cells.

作者信息

Wang Zhanhuai, Tan Yinuo, Yu Wei, Zheng Shu, Zhang Suzhan, Sun Lifeng, Ding Kefeng

机构信息

Department of Surgical Oncology, Second Affiliated Hospital of School of Medicine, Zhejiang University, Jiefang Road 88, Hangzhou, Zhejiang Province, 310009, China.; The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Jiefang Road 88, Hangzhou, Zhejiang Province, 310009, China.

The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Jiefang Road 88, Hangzhou, Zhejiang Province, 310009, China.

出版信息

Int J Biol Sci. 2017 Feb 25;13(3):339-348. doi: 10.7150/ijbs.17680. eCollection 2017.

Abstract

Cancer microenvironment is composed of numerous components that can support cancer cell proliferation, promote cancer progression and contribute to cancer treatment resistance. The major components of caner microenvironment are fibroblasts, endothelial cells, immune cells as well as cytokines, chemokines, and extracellular matrix (ECM) all of which surround tumor cells as the core and cross talk with each other. Among them, cancer-associated fibroblasts (CAFs) play an important role in promoting cancer progression by secreting various pro-inflammatory factors. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate protein expression both in cancer cell and normal stromal cells. Changes of miRNAs expression in cancer-associated fibroblasts can be induced both by cancer cells and other stromal cells. This change can arise through direct interaction or by secreted paracrine factors or even by secreted miRNAs. The desregulated miRNAs in cancer-associated fibroblasts then enhance the CAFs phenotype and assist their cancer promotion ability. Explore the regulatory function of miRNAs in the complex communication between cancer cells and cancer microenvironment is important to understand the process of tumor progression and may help to develop new therapeutic strategies. This review provides an updated content of latest research advances about the relevance of miRNAs in the interaction between cancer cells and the CAFs. We will describe miRNAs which are differential expressed by NFs and CAFs, their function in regulating fibroblasts activation as well as miRNAs expressed in CAFs as prognostic factors in cancer stroma in recent studies. We will also discuss miRNA as an important player in CAFs mediated regulation of cancer progression and metastasis cancer metabolism, cancer stem cell property and chemoresistance.

摘要

癌症微环境由众多能够支持癌细胞增殖、促进癌症进展并导致癌症治疗耐药的成分组成。癌症微环境的主要成分包括成纤维细胞、内皮细胞、免疫细胞以及细胞因子、趋化因子和细胞外基质(ECM),所有这些都以肿瘤细胞为核心环绕并相互作用。其中,癌症相关成纤维细胞(CAFs)通过分泌各种促炎因子在促进癌症进展中发挥重要作用。微小RNA(miRNAs)是小的非编码RNA,在癌细胞和正常基质细胞中均对蛋白质表达起负调控作用。癌细胞和其他基质细胞均可诱导癌症相关成纤维细胞中miRNAs表达的变化。这种变化可通过直接相互作用、分泌的旁分泌因子甚至分泌的miRNAs产生。癌症相关成纤维细胞中失调的miRNAs随后增强CAFs表型并辅助其促进癌症的能力。探索miRNAs在癌细胞与癌症微环境复杂通讯中的调控功能对于理解肿瘤进展过程很重要,并且可能有助于开发新的治疗策略。本综述提供了关于miRNAs在癌细胞与CAFs相互作用中相关性的最新研究进展的更新内容。我们将描述由正常成纤维细胞(NFs)和CAFs差异表达的miRNAs、它们在调节成纤维细胞活化中的功能以及近期研究中在癌症基质中作为预后因素在CAFs中表达的miRNAs。我们还将讨论miRNA作为CAFs介导的癌症进展和转移、癌症代谢、癌症干细胞特性及化疗耐药调节中的重要参与者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9011/5370441/d3ba2f6b8564/ijbsv13p0339g001.jpg

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