肝癌干细胞的研究热点及其临床意义

背景：肝癌是否存在肿瘤干细胞目前还没有明确答案。已发现一些具有特异性的细胞标志物，但需进一步验证筛选。信号传导调控在肝癌的发生发展和转移复发过程中究竟起到何种作用，是目前研究的重要课题。而针对肝癌对放化疗抵抗特性，也有许多研究分析值得关注。 目的：复习相关文献，就肝癌干细胞起源、干细胞标志物、信号传导调控、对治疗抵抗原理及相应治疗策略等方面进行综述。 方法：以“cancer stem cells, hepatocellular carcinoma, markers, therapy”为检索词，应用计算机检索Pubmed数据库1996-01/2010-01关于肝癌干细胞标识、分子调控及治疗的文献；以“肿瘤干细胞，肝细胞癌，标志物，治疗”为检索词，机检索重庆维普数据库、清华同方数据库1996-01/2010-01相关文献。纳入30篇符合标准的文献进行分析讨论。 结果与结论：研究表明肝癌组织中存在肿瘤干细胞特性的细胞亚群，其来源可能是多源的，并与肿瘤转移特性密切相关。目前已发现的肝癌干细胞标志物如OV6、AFP、c-kit、EpCAM和CD90等，对干细胞识别筛选起到重要作用。研究表明Wnt，Shh，Notch和PI3K/AKT/mTOR等信号传导途径对肝癌干细胞发挥重要的调控作用。针对干细胞抗药特性，采取分子靶向治疗、分化治疗和抗体治疗，对肝癌治疗取得了初步疗效，需要进一步深入研究。

Research focus and clinical significance of hepatocarcinoma stem cells

BACKGROUND:It remains unclear whether hepatocellular carcinoma (HCC) processes cancer stem cells. Some specific cell markers were found, but required further verification. The effects of signal conduction regulation in the process of occurrence, development, transfer and recurrence of HCC are a key topic in present research. However, chemotherapy and radiotherapy against properties of HCC also need further attention. OBJECTIVE:To review hepatocarcinoma stem cell source, stem cell marker, signal conduction regulation, therapeutic resistence principle and corresponding therapeutic strategy. METHODS:The key words were “cancer stem cells, hepatocellular carcinoma, markers, therapy”. We retrieved PubMed database for articles on hepatocarcinoma stem cell marker, molecular regulation and treatment published from January 1996 to January 2010. Vip Database and Tsinghua Tongfang Full Text Database were searched using the same key words for articles published from January 1996 to January 2010. Finally, 30 articles were included in accordance with inclusion criteria. RESULTS AND CONCLUSION: Studies have suggested that there is cell subpopulation with cancer stem cell properties. Its source is multiple and associates with tumor metastasis. At present, hepatocarcinoma stem cell markers such as OV6, AFP, c-kit, EpCAM and CD90 play important roles in identifying and screening stem cells. Studies indicated that cancer related signaling pathways, such as the Wnt, Shh, Notch and PI3K/AKT/mTOR pathways, play an important role in the regulation of hepatocarcinoma stem cells. For drug resistant properties of stem cells, molecular target therapy, differentiation therapy and antibody therapy are used for treating hepatoma and obtain primary curative effect, but these require further investigation.