Enhanced Expression of Cancer Testis Antigen Genes in Glioma Stem Cells
Enhanced Expression of Cancer Testis Antigen Genes in Glioma Stem Cells
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DOI：
10.1002/mc.20614
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发表时间：
2010-06-01
影响因子：
4.6
通讯作者：
Shimizu, Keiji
中科院分区：
文献类型：
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作者：
Yawata, Toshio;Nakai, Eiichi;Shimizu, Keiji
癌症干细胞是有效治疗的重要靶点，因为它们显示出致瘤性、化学抗性和放射抗性。我们从神经胶质瘤细胞系和组织中分离出肿瘤干细胞，并检测了肿瘤睾丸抗原（CIA）基因作为肿瘤疫苗治疗潜在靶分子的表达。与分化细胞相比，CIA基因在肿瘤干细胞中高度且频繁地表达。此外，CIA基因启动子区域的组蛋白乙酰化水平在癌症干细胞中较高，在分化细胞中较低，而启动子区域的DNA甲基化分析显示癌症干细胞中甲基化不足。细胞之间的这种表观遗传差异导致CIA基因在肿瘤块中的异质性表达，肿瘤块由不同分化水平的细胞组成。此外，HLA I类抗原的表达水平不受分化状态的影响，这表明CIA基因可能作为表面抗原存在于肿瘤干细胞中。总之，这些发现表明，CIA基因可能是针对胶质瘤患者癌症干细胞的靶向疫苗治疗的有吸引力的候选者。(C)2010 Wiley-Liss，Inc.
Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CIA) genes as potential target molecules for cancer vaccine therapy. CIA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CIA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CIA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CIA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CIA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients. (C) 2010 Wiley-Liss, Inc.