脑胶质瘤中疱疹病毒相关性泛素特异性蛋白酶与CD133的表达及其相关性  

Expressiom of herpesvirus-associated ubiquitin-specific protease and CD133 in gliomas and their correlation

作　　者：程传东 牛朝诗 杨洋 

机构地区：[1]安徽医科大学附属省立医院神经外科脑功能与脑疾病安徽省重点实验室安徽省脑立体定向神经外科研究所,合肥230001

出　　处：《中华实验外科杂志》2014年第9期1892-1894,I0001,I0002,共5页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81172407）

摘　　要：目的 研究人脑胶质瘤中疱疹病毒相关性泛素特异性蛋白酶（HAUSP）与脑肿瘤干细胞（BTSCs）标志物CD133之间表达的关系,并探讨其在脑胶质瘤发生发展中的意义.方法 （1）取人脑胶质瘤组织标本72例,采用免疫组织化学染色检测HAUSP、CD133的表达,比较不同级别胶质瘤HAUSP＋细胞和CD133＋细胞所占百分比并分析其与胶质瘤级别的相关性.（2）血清剥夺法从U87胶质瘤细胞株分离培养BTSCs,通过全反式维甲酸（ATRA）诱导分化,免疫细胞荧光双重染色观察HAUSP及CD133在不同时期表达.结果 Ⅱ～Ⅳ级胶质瘤中HAUSP＋细胞率分别为（25.9±11.3）％、（49.8±19.8）％、（63.7±20.4）％;CD133＋细胞率分别为（12.60±3.49）％、（18.90±5.81）％、（24.80±7.54）％,不同级别胶质瘤中HAUSP＋细胞、CD133＋细胞百分比差异均有统计学意义（P＜0.05）,高级别组胶质瘤中HAUSP＋细胞、CD133＋细胞表达水平高于低级别组,差异有统计学意义（P＜0.05）;HAUSP＋表达和CD133＋表达呈正相关（r=0.915,P＜0.01）;随着U87胶质瘤干细胞分化,HAUSP、CD133表达逐渐减少.结论 HAUSP与干细胞标志物CD133之间有明显的相关性.HAUSP在维持脑胶质瘤干细胞未分化或低分化的状态中可能起到重要作用.Objective To explore the relationship between herpesvirus-associated ubiquitin-specific protease （HAUSP） and CD133 in gliomas of different pathological grades,and discuss the significance of HAUSP expression in glioma development.Methods The expression of HAUSP and CD133 were detected by immunohistochemistry in the specimens of 72 cases of glioma tissues.Brain tumor stem cells （BTSCs） were isolated from glioma celI line U87 and cultured in simplified serum-free neural stem cell medium by nanosphere suspension culture method spheres,and purified continuously through the monoclonal formation experiment.All-trans retinoic acid （ATRA） was used to induce the differentiation of BTSCs.Double immunofluorescence staining was used to detect the co-expressions of HAUSP and CD133.Results The percentages of HAUSP ＋ and CD133 ＋ in gliomas of grade Ⅱ-Ⅳ were （25.9 ± 11.3） %,（49.8±19.8）%,（63.7±20.4）%,and （12.60±3.49）%,（18.90±5.81）%,（24.80±7.54）% respectively,which were significantly different （P 〈 0.05）,and the expressions of HAUSP＋,CD133 ＋cells in gliomas of grade Ⅲ and Ⅳ were significantly higher than those in glioma of grade Ⅱ （P 〈 0.05）.The HAUSP＋ expression and CD133 ＋ expression were positively correlated （r =0.915,P 〈 0.01）.HAUSP ＋ and CD133 ＋ expressions were reduced followed as the differentiation of BTSCs.Conclusion HAUSP and stem cell marker CD133 has a significant correlation,and they enjoy significant co-expressions in cellular level.HAUSP may play a crucial role in the maintenance of glioma stem cells undifferentiated or poorly differentiated state.

关 键 词：神经胶质瘤 肿瘤干细胞 免疫组织化学 疱疹病毒相关性泛素特异性蛋白酶 CD133 

分 类 号：R739.41[医药卫生—肿瘤]