Lipopolysaccharide promotes tumorigenicity of hepatic progenitor cells by promoting proliferation and blocking normal differentiation
Lipopolysaccharide promotes tumorigenicity of hepatic progenitor cells by promoting proliferation and blocking normal differentiation
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脂多糖通过促进增殖和阻断正常分化来促进肝祖细胞的致瘤性
DOI：
10.1016/j.canlet.2016.10.044
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发表时间：
2017-02-01
期刊：
影响因子：
9.7
通讯作者：
Wei, Li-Xin
中科院分区：
文献类型：
--
作者：
Li, Xiao-Yong;Yang, Xue;Wei, Li-Xin
肝祖细胞（HPCs）是一种双潜能干细胞，能够分化为成熟的肝细胞或胆管上皮细胞（BECs）。它们被认为参与肝脏损伤的修复以及肝癌的发生。它们的生理特性与它们所处的微环境密切相关。脂多糖（LPS）是肝脏病理微环境的一个重要组成部分，储存在肝脏中，并在多种肝脏疾病中影响多种类型的细胞。肝祖细胞也可能受到LPS的影响。在本文中，将小鼠胚胎13.5天的E - 钙黏蛋白（+）胎肝细胞分离出来作为小鼠肝祖细胞（mHPCs）。在体内和体外，LPS条件下mHPCs的增殖均得到促进。此外，LPS增强了mHPCs的集落形成能力，并阻碍它们分化为成熟肝细胞以及胆管样结构的形成。更重要的是，长期用LPS处理促进了mHPCs在裸鼠中的致瘤性。因此，我们得出结论：LPS可能促进mHPCs的异常增殖并限制其正常分化。mHPCs长期暴露于LPS会增加肿瘤形成的风险。这些数据为LPS、肝祖细胞命运和肿瘤发生之间的联系提供了见解，并为肝祖细胞与其微环境之间的关系提供了新的视角。（C）2016作者。由爱思唯尔爱尔兰有限公司出版。
Hepatic progenitor cells (HPCs) are bipotential stem cells that can differentiate into mature hepatocytes or biliary epithelial cells (BECs). They are thought to be involved in repair of liver injury and the incidence of hepatic carcinoma. Their physiology is closely associated with the microenvironment where they reside. Lipopolysaccharide (LPS), an important component of the hepatic pathological microenvironment, is stored in the liver and affects many types of cells in various hepatosis. HPCs may also be influenced by LPS. In this paper, mouse ED13.5 E-cadherin(+) foetal liver cells were isolated as mouse hepatic progenitor cells (mHPCs). Proliferation of mHPCs was promoted under LPS conditions both in vivo and in vitro. Moreover, LPS enhanced colony formation ability of mHPCs, and blocked them differentiation into mature hepatocytes and formation of a bile duct-liked structure. More importantly, long-term treatment with LPS promoted tumorigenesis of mHPCs in nude mice. Thus, we conclude that LPS may promote aberrant proliferation of mHPCs and restrict their normal differentiation. Long-term exposure of mHPCs to LPS increased the risk of tumour formation. These data provide insight into the links between LPS, HPCs fate, and tumorigenesis, and present novel insight into the relationship between HPCs and their microenvironment. (C) 2016 The Author(s). Published by Elsevier Ireland Ltd.