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Fibroblast Reprogramming in Gastrointestinal Cancer.
Frontiers in Cell and Developmental Biology ( IF 4.6 ) Pub Date : 2020-06-23 , DOI: 10.3389/fcell.2020.00630
Maria-Theodora Melissari 1 , Niki Chalkidi 1 , Michalis E Sarris 1 , Vasiliki Koliaraki 1
Affiliation  

Gastrointestinal cancers are a significant cause of cancer mortality worldwide and have been strongly linked with chronic inflammation. Current therapies focus on epithelial/cancer cells; however, the importance of the tumor microenvironment in the development and treatment of the disease is also now well established. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment, and are actively participating in tumor initiation, promotion and metastasis. They structurally and functionally affect cancer cell proliferation, tumor immunity, angiogenesis, extracellular matrix remodeling and metastasis through a variety of signaling pathways. CAFs originate predominantly from resident mesenchymal cells, which are activated and reprogrammed in response to cues from cancer cells. In recent years, chronic inflammation of the gastrointestinal tract has also proven an important driver of mesenchymal cell activation and subsequent CAF development, which in turn are capable of regulating the transition from acute to chronic inflammation and cancer. In this review, we will provide a concise overview of the mechanisms that drive fibroblast reprogramming in cancer and the recent advances on the downstream signaling pathways that regulate the functional properties of the activated mesenchyme. This new mechanistic insight could pave the way for new therapeutic strategies and better prognosis for cancer patients.



中文翻译:

胃肠道癌中的成纤维细胞重编程。

胃肠道癌症是全世界癌症死亡的重要原因,并且与慢性炎症密切相关。目前的治疗方法集中在上皮/癌细胞上。然而,肿瘤微环境在该疾病的发展和治疗中的重要性现在也已被确立。癌症相关的成纤维细胞(CAF)是肿瘤微环境的主要组成部分,并积极参与肿瘤的发生,促进和转移。它们在结构和功能上通过多种信号通路影响癌细胞的增殖,肿瘤免疫力,血管生成,细胞外基质重塑和转移。CAF主要来自常驻间充质细胞,这些间充质细胞会响应癌细胞的信号而被激活并重新编程。最近几年,胃肠道的慢性炎症也已被证明是间充质细胞活化和随后的CAF形成的重要驱动力,而CAF的发展又能够调节从急性到慢性炎症和癌症的转变。在这篇综述中,我们将简要概述在癌症中驱动成纤维细胞重编程的机制,以及调节活化间充质功能特性的下游信号通路的最新进展。这种新的机理见解可以为癌症患者的新治疗策略和更好的预后铺平道路。我们将简要概述癌症中驱动成纤维细胞重编程的机制,以及调节活化间充质功能特性的下游信号通路的最新进展。这种新的机理见解可以为癌症患者的新治疗策略和更好的预后铺平道路。我们将简要概述癌症中驱动成纤维细胞重编程的机制,以及调节活化间充质功能特性的下游信号通路的最新进展。这种新的机理见解可以为癌症患者的新治疗策略和更好的预后铺平道路。

更新日期:2020-07-15
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