Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China.
Department of Clinical Oncology, The University of Hong Kong, Hong Kong 999077, China.
Int J Mol Sci. 2022 Oct 14;23(20):12327. doi: 10.3390/ijms232012327.
Hepatocellular carcinoma (HCC) remains the most predominant type of liver cancer with an extremely poor prognosis due to its late diagnosis and high recurrence rate. One of the culprits for HCC recurrence and metastasis is the existence of cancer stem cells (CSCs), which are a small subset of cancer cells possessing robust stem cell properties within tumors. CSCs play crucial roles in tumor heterogeneity constitution, tumorigenesis, tumor relapse, metastasis, and resistance to anti-cancer therapies. Elucidation of how these CSCs maintain their stemness features is essential for the development of CSCs-based therapy. In this review, we summarize the present knowledge of intrinsic molecules and signaling pathways involved in hepatic CSCs, especially the CSC surface markers and associated signaling in regulating the stemness characteristics and the heterogeneous subpopulations within the CSC pool. In addition, we recapitulate the effects of crucial extrinsic cellular components in the tumor microenvironment, including stromal cells and immune cells, on the modulation of hepatic CSCs. Finally, we synopsize the currently valuable CSCs-targeted therapy strategies based on intervention in these intrinsic and extrinsic molecular mechanisms, in the hope of shedding light on better clinical management of HCC patients.
肝细胞癌 (HCC) 仍然是最主要的肝癌类型，由于其诊断较晚和高复发率，预后极差。 HCC 复发和转移的罪魁祸首之一是癌症干细胞 (CSC) 的存在，CSC 是肿瘤内具有强大干细胞特性的一小部分癌细胞。 CSCs 在肿瘤异质性构成、肿瘤发生、肿瘤复发、转移和对抗癌治疗的耐药性中起着至关重要的作用。阐明这些 CSCs 如何维持其干细胞特性对于基于 CSC 的治疗的发展至关重要。在这篇综述中，我们总结了涉及肝 CSC 的内在分子和信号通路的现有知识，特别是 CSC 表面标记物和相关信号通路在调节干细胞特性和 CSC 池内异质亚群中的作用。此外，我们回顾了肿瘤微环境中关键细胞外成分（包括基质细胞和免疫细胞）对肝 CSC 调节的影响。最后，我们综合了目前基于干预这些内在和外在分子机制的有价值的 CSC 靶向治疗策略，希望为 HCC 患者的临床管理提供新的思路。
