Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Semin Oncol. 2012 Aug;39(4):461-72. doi: 10.1053/j.seminoncol.2012.05.011.
Solid tumors are thought to contain cancer stem cells (CSCs) as a distinct population responsible for tumor relapse and metastasis due to their abilities to self-renew, differentiate, and give rise to a new tumor in local or distant organs. CSCs have been identified in many tumor types, including hepatocellular carcinoma (HCC), the fifth most common and third most deadly malignancy with observable heterogeneity. Numerous studies have shown that hepatic CSCs could be enriched via different cell surface markers, eg, CD13, CD24, CD44, CD90, CD133, EpCAM (CD326), and OV6. They also could be identified through functional assays such as isolating the side population cells by Hoechst dye staining or screening cells with a high activity of aldehyde dehydrogenase. Functional characterization of hepatic CSCs has revealed several deregulated signaling pathways, such as Wnt/β-catenin, AKT, transforming growth factor-beta (TGF-β), interleukin (IL)-6/STAT3 pathways to be critical in inducing "stemness" of HCC and in promoting self-renewal, tumorigenicity, and chemoresistance. An increased understanding of hepatic CSC biology facilitated the development of new diagnostic, prognostic, and therapeutic strategies for improving HCC clinical management. In this review, we summarize recent evidence including the identification of the hepatic CSC and its underlying biological mechanisms, and discuss the potential clinical implications in HCC.
实体瘤被认为包含癌症干细胞 (CSC)，作为一个独特的群体，由于其自我更新、分化的能力，并在局部或远处器官产生新的肿瘤，导致肿瘤复发和转移。在许多肿瘤类型中，包括肝癌 (HCC)，已经鉴定出 CSC，HCC 是第五种最常见和第三种最致命的恶性肿瘤，具有可观察的异质性。许多研究表明，肝 CSC 可以通过不同的细胞表面标志物富集，例如 CD13、CD24、CD44、CD90、CD133、EpCAM（CD326）和 OV6。它们也可以通过功能测定来鉴定，例如通过 Hoechst 染料染色分离侧群细胞，或筛选具有高醛脱氢酶活性的细胞。肝 CSC 的功能特征揭示了几个失调的信号通路，如 Wnt/β-catenin、AKT、转化生长因子-β (TGF-β)、白细胞介素 (IL)-6/STAT3 通路，在诱导 HCC 的“干性”和促进自我更新、致瘤性和化疗耐药性方面至关重要。对肝 CSC 生物学的深入了解促进了新的诊断、预后和治疗策略的发展，以改善 HCC 的临床管理。在这篇综述中，我们总结了最近的证据，包括肝 CSC 的鉴定及其潜在的生物学机制，并讨论了其在 HCC 中的潜在临床意义。
