The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer.
The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer.
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DOI：
10.1146/annurev-pathol-052016-100322
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发表时间：
2017-01-24
期刊：
影响因子：
--
通讯作者：
Schwabe RF
中科院分区：
文献类型：
--
作者：
Affo S;Yu LX;Schwabe RF
肝癌是全球癌症死亡率的第二大原因，每年造成超过70万人死亡。由于基因组改变的广泛前景和靶向肿瘤细胞的有限治疗成功，最近的重点是更好地理解和可能靶向肝肿瘤发展的微环境。肝癌的一个独特特征是其与肝纤维化密切相关。超过80%的肝细胞癌（HCC）发生在纤维化或坏死的肝脏中，这表明肝纤维化在肝脏的癌前环境（PME）中起着重要作用。相反，胆管癌（CCA）的特征在于强烈的结缔组织增生，其通常响应于肿瘤而发生，表明癌症相关成纤维细胞（CAF）和纤维化在其肿瘤微环境（TME）中的关键作用。在这里，我们讨论了肌成纤维细胞，CAFs和纤维化的功能贡献HCC和CCA的发展在肝PME和TME，专注于肌成纤维细胞和细胞外基质相关的生长因子，纤维化相关的免疫抑制途径，以及机械敏感的信号级联被激活的组织硬度增加。更好地了解肌成纤维细胞在HCC和CCA发展和进展中的作用可能为靶向这些细胞用于肿瘤预防或治疗提供基础。
Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. More than 80% of hepatocellular carcinomas (HCCs) develop in fibrotic or cirrhotic livers, suggesting an important role of liver fibrosis in the premalignant environment (PME) of the liver. Cholangiocarcinoma (CCA), in contrast, is characterized by a strong desmoplasia that typically occurs in response to the tumor, suggesting a key role of cancer-associated fibroblasts (CAFs) and fibrosis in its tumor microenvironment (TME). Here, we discuss the functional contributions of myofibroblasts, CAFs, and fibrosis to the development of HCC and CCA in the hepatic PME and TME, focusing on myofibroblast- and extracellular matrix—associated growth factors, fibrosis-associated immunosuppressive pathways, as well as mechanosensitive signaling cascades that are activated by increased tissue stiffness. Better understanding of the role of myofibroblasts in HCC and CCA development and progression may provide the basis to target these cells for tumor prevention or therapy.
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