Clinical implications of cancer stem cell biology in hepatocellular carcinoma.
Clinical implications of cancer stem cell biology in hepatocellular carcinoma.
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DOI：
10.1053/j.seminoncol.2012.05.011
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发表时间：
2012-08
影响因子：
4
通讯作者：
Wang XW
中科院分区：
文献类型：
--
作者：
Ji J;Wang XW
实体肿瘤被认为含有癌症干细胞（CSCs），由于它们具有自我更新、分化和在局部或远处器官产生新肿瘤的能力，因此它们是肿瘤复发和转移的一个独特群体。CSCs已在许多肿瘤类型中被发现，包括肝细胞癌（HCC），这是第五常见和第三致命的恶性肿瘤，具有可观察到的异质性。大量研究表明，肝CSCs可以通过不同的细胞表面标记物富集，如CD13、CD24、CD44、CD90、CD133、EpCAM （CD326）和OV6。它们也可以通过功能分析来鉴定，如用赫斯特染色法分离侧群细胞或筛选具有高活性醛脱氢酶的细胞。肝CSCs的功能表征揭示了几种失调的信号通路，如Wnt/β-catenin、AKT、tgf - β、IL-6/STAT3通路，在诱导HCC“干性”、促进自我更新、致瘤性和化疗耐药中起关键作用。对肝CSC生物学的进一步了解有助于开发新的诊断和预后治疗策略，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CSCs的鉴定及其潜在的生物学机制，并讨论了HCC的潜在临床意义。
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, e.g., CD13, CD24, CD44, CD90, CD133, EpCAM (CD326), and OV6. They could also 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, TGF-beta, IL-6/STAT3 pathways to be critical in inducing “stemness” of HCC and in promoting self-renewal, tumorigenicity and chemoresistance. An increased understanding of the hepatic CSC biology shed light on the development of new diagnostic, prognostic therapeutic strategies in improving HCC clinical management. In this review, we summarized recent evidence including the identification of hepatic CSCs and its underlying biological mechanisms, and discussed potential clinical implications in HCC.
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