肝细胞癌(HCC)是由肝脏引起的主要原发性癌症,是全球癌症相关死亡率的主要原因之一。HCC的细胞起源一直是一个非常感兴趣的话题,由于关于它是否起源于肝细胞的矛盾发现,胆管细胞,或兼性干细胞。这些细胞类型在肝损伤期间都会发生变化,关于它们对肝脏再生反应的贡献存在争议。大多数HCC出现在病毒性肝炎慢性肝损伤的背景下,脂肪肝,酒精,和环境暴露。损伤的标志是肝实质的变化,如肝细胞再生结节,胆管细胞变化,导致纤维化和肝硬化的肌成纤维细胞的扩张,和炎症细胞浸润,所有这些都可能导致癌症的发生。解决HCC的细胞起源是确定触发它的最早事件的关键。在这里,我们回顾了有关再生肝脏和HCC中起源细胞的数据,以及这些发现对预防和治疗的意义。我们还回顾了儿童肝癌和其他罕见肝癌的起源。
Hepatocellular carcinoma (HCC) is the predominant primary cancer arising from the liver and is one of the major causes of cancer-related mortality worldwide. The cellular origin of HCC has been a topic of great interest due to conflicting findings regarding whether it originates in hepatocytes, biliary cells, or facultative stem cells. These cell types all undergo changes during liver injury, and there is controversy about their contribution to regenerative responses in the liver. Most HCCs emerge in the setting of chronic liver injury from viral hepatitis, fatty liver disease, alcohol, and environmental exposures. The injuries are marked by liver parenchymal changes such as hepatocyte regenerative nodules, biliary duct cellular changes, expansion of myofibroblasts that cause fibrosis and cirrhosis, and inflammatory cell infiltration, all of which may contribute to carcinogenesis. Addressing the cellular origin of HCC is the key to identifying the earliest events that trigger it. Herein, we review data on the cells of origin in regenerating liver and HCC and the implications of these findings for prevention and treatment. We also review the origins of childhood liver cancer and other rare cancers of the liver.