Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma.

Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma.
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鉴定癌症相关成纤维细胞作为肝细胞癌的新兴靶点。

DOI:
10.1186/s13578-020-00488-y
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发表时间:
2020-10-31
期刊:
影响因子:
7.5
通讯作者:
Zheng W
Zheng W
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang J;Gu C;Song Q;Zhu M;Xu Y;Xiao M;Zheng W

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肿瘤微环境(TME)是一个复杂的多细胞功能区室,包括成纤维细胞、肌成纤维细胞、内皮细胞、免疫细胞和细胞外基质(ECM)成分。微环境为肝细胞癌(HCC)的发生、生长和扩散提供了最佳条件。癌相关成纤维细胞(CAFs)作为肿瘤微环境中重要而丰富的成分之一,与肝癌的发生发展密切相关。CAFs通过分泌多种生长因子和细胞因子,参与ECM重塑、干细胞特征、血管生成、免疫抑制和血管生成拟态(VM),从而促进HCC的发生和发展。为了抑制CAFs启动的HCC进展,目前的策略包括靶向特异性标记物、工程化具有肿瘤抑制表型的CAFs、耗尽CAFs的前体以及抑制CAFs的分泌或下游信号传导。在这篇综述中,我们更新了对HCC中CAFs的新认识,特别强调细胞起源,表型,生物学功能和靶向策略。它为HCC治疗的靶向CAF提供了见解。
The tumor microenvironment (TME) is a complex multicellular functional compartment that includes fibroblasts, myofibroblasts, endothelial cells, immune cells, and extracellular matrix (ECM) elements. The microenvironment provides an optimum condition for the initiation, growth, and dissemination of hepatocellular carcinoma (HCC). As one of the critical and abundant components in tumor microenvironment, cancer-associated fibroblasts (CAFs) have been implicated in the progression of HCC. Through secreting various growth factors and cytokines, CAFs contribute to the ECM remodeling, stem features, angiogenesis, immunosuppression, and vasculogenic mimicry (VM), which reinforce the initiation and development of HCC. In order to restrain the CAFs-initiated HCC progression, current strategies include targeting specific markers, engineering CAFs with tumor-suppressive phenotype, depleting CAFs’ precursors, and repressing the secretions or downstream signaling. In this review, we update the emerging understanding of CAFs in HCC, with particular emphasis on cellular origin, phenotypes, biological functions and targeted strategies. It provides insights into the targeting CAFs for HCC treatment.
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