氨肽酶N:肝癌干细胞的治疗靶点

Aminopeptidase N:a therapeutic target in human liver cancer stem cells

肝癌干细胞(liver cancer stem cells,LCSC)在肝癌的发生发展过程中起重要作用。LCSC具有自我更新和肿瘤起始能力,并且处于静息期、慢生长阶段或低分化状态,与肝癌耐药、复发、转移等关系密切。为研究LCSC的生长特点,可以通过特异性标志物分选法鉴别分选LCSC。早期研究表明,细胞表面抗原分子CD133、细胞黏附分子免疫球蛋白(CD90、CD44、CD24)、上皮细胞黏附分子(epithelial cell adhesion molecule,EpCAM)等均可作为LCSC的特异性标志物。近年发现肝癌中表达氨肽酶N(aminopeptidase N,APN,CD13)的细胞具有干细胞的生物学特性,认为CD13可作为LCSC的特异性标志物。本文将介绍CD13的结构和主要功能、LCSC的来源和鉴别、CD13+细胞在肝癌中的作用以及联合用药治疗肝癌等。

Liver cancer stem cells（LCSC）play the critical role in hepatocellular carcinoma development and maintenance.They are generally dormant or slowly cycling tumor cells that have the ability to reconstitute tumors. LCSC associate closely with tumor resistance to chemo/radiation therapy, tumor relapse and metastasis, and can be identified and separated with some special surface markers from hepatocellular carcinoma, such as CD133, CD90, CD44, CD24 and EpCAM to investigate the biological behaviors of them. Early studies showed that these markers can be regarded as special surface markers of liver cancer stem cells.Recent studies found that aminopeptidase N（APN,CD13＋）cells in hepatocellular carcinoma have biological characteristics of stem cells and demonstrated that CD13 is a marker for semiquiescent CSC in human liver cancer cell lines and clinical samples and that targeting these cells might provide a way to treat this disease. In this review,we introduce the structure and the main function of CD13,liver cancer stem cells source and identification,CD13＋CSC in hepatocellular carcinoma and combination therapy in the treatment of liver cancer.