Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment
Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment
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DOI：
10.1172/jci77995
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发表时间：
2015-10-01
影响因子：
15.9
通讯作者：
Schwabe, Robert F.
中科院分区：
文献类型：
--
作者：
Mu, Xueru;Espanol-Suner, Regina;Schwabe, Robert F.
在许多器官中，包括肠和皮肤，癌症起源于干细胞或祖细胞室。尽管它的命名，肝细胞癌（HCC）的细胞起源仍然难以捉摸。与大多数器官相比，肝脏缺乏用于器官维持的明确的干细胞群。先前的研究表明，胆道腔内的肝细胞和兼性祖细胞都能产生HCC。由于具有祖细胞特征的HCC预后较差，因此了解HCC的起源具有临床意义。在这里，我们使用互补的命运追踪方法来标记小鼠肝癌发生中的祖细胞/胆道室和肝细胞。在遗传毒性和遗传模型中，hcc完全来自肝细胞，而不是来自祖细胞/胆道室。肿瘤内的细胞角蛋白19、A6和甲胎蛋白阳性细胞来源于肝细胞。总之，肝细胞代表小鼠HCC的起源细胞，祖细胞标记不反映祖细胞起源，而是肝细胞来源的肿瘤细胞的去分化。
In many organs, including the intestine and skin, cancers originate from cells of the stem or progenitor compartment. Despite its nomenclature, the cellular origin of hepatocellular carcinoma (HCC) remains elusive. In contrast to most organs, the liver lacks a defined stem cell population for organ maintenance. Previous studies suggest that both hepatocytes and facultative progenitor cells within the biliary compartment are capable of generating HCC. As HCCs with a progenitor signature carry a worse prognosis, understanding the origin of HCC is of clinical relevance. Here, we used complementary fate-tracing approaches to label the progenitor/biliary compartment and hepatocytes in murine hepatocarcinogenesis. In genotoxic and genetic models, HCCs arose exclusively from hepatocytes but never from the progenitor/biliary compartment. Cytokeratin 19-, A6- and alpha-fetoprotein-positive cells within tumors were hepatocyte derived. In summary, hepatocytes represent the cell of origin for HCC in mice, and a progenitor signature does not reflect progenitor origin, but dedifferentiation of hepatocyte-derived tumor cells.