Oncostatin M promotes hepatic progenitor cell activation and hepatocarcinogenesis via macrophage-derived tumor necrosis factor-alpha
Oncostatin M promotes hepatic progenitor cell activation and hepatocarcinogenesis via macrophage-derived tumor necrosis factor-alpha
复制标题
制瘤素 M 通过巨噬细胞衍生的肿瘤坏死因子-α 促进肝祖细胞活化和肝癌发生。
DOI：
10.1016/j.canlet.2021.05.039
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发表时间：
2021
期刊：
影响因子：
9.7
通讯作者：
Wei Lixin
中科院分区：
文献类型：
--
作者：
Yang Xue;Shao Changchun;Duan Lixia;Hou Xiaojuan;Huang Yihua;Gao Lu;Zong Chen;Liu Wenting;Jiang Jinghua;Ye Fei;Shi Junxia;Zhao Qiudong;Wu Dong;Wei Lixin
肝细胞癌（HCC）通常发生在慢性肝损伤的晚期。抑瘤素M（OSM）是一种在肝硬化和肝癌患者中高表达的肿瘤相关细胞因子，然而，其在肝癌发生中的作用尚未明确阐明。在这项研究中，我们研究了OSM对N-二乙基亚硝胺诱导的大鼠肝癌模型中肝癌发生的影响。OSM过表达显著增加了肿瘤结节的数量，缩短了大鼠的总体生存期。值得注意的是，OSM在体内促进HPC活化，但在体外不直接调节HPC细胞系的增殖。此外，OSM诱导肿瘤坏死因子-α（TNF-α）分泌和CD 68+巨噬细胞积聚，这与HPC活化呈正相关。TNF-α或巨噬细胞耗竭抑制OSM对肝癌发生和HPC活化的促进作用。此外，OSM在HCC瘤周组织中的表达与患者的不良总生存率呈正相关。总之，OSM通过调节肝脏炎症环境在肝癌发生中发挥重要作用。因此，OSM可作为HCC预防和治疗的潜在靶点或作为HCC预后的指标。
Hepatocellular carcinoma (HCC) usually occurs at the late stage of chronic liver injury. Oncostatin M (OSM) is a tumor-associated cytokine highly expressed in cirrhosis and HCC patients; however, its role in hepatocarcinogenesis has not been clearly elucidated. In this study, we investigated the effect of OSM on HCC occurrence in a rat model ofN-diethylnitrosamine-induced HCC. OSM overexpression significantly increased the number of tumor nodules and shortened the overall survival of the rats. Notably, OSM promoted HPC activationin vivobut did not directly regulate the proliferation of the HPC cell linein vitro. Further, OSM induced tumor necrosis factor-α (TNF-α) secretion and CD68+macrophage accumulation, which were positively correlated with HPC activation. Additionally, TNF-α or macrophage depletion inhibited the promoting effect of OSM on hepatocarcinogenesis and HPC activation. Furthermore, OSM expression in the peritumoral tissues of HCC was positively correlated with poor overall survival of patients. In conclusion, OSM plays an important role in hepatocarcinogenesis by regulating the liver inflammation environment. Hence, OSM could be used as a potential target for HCC prevention and therapy or as an indicator of HCC prognosis.