脑肿瘤干细胞壁龛的病理学特性研究  

The Pathological Characteristics of Niches for Glioma Stem Cells

作　　者：李明武[1,2] 牛朝诗[1,2] 董永飞[1,2] 高歌[1,2] 梅加明[1,2] 傅先明[1,2] 

机构地区：[1]安徽医科大学附属省立医院神经外科 [2]安徽省立体定向神经外科研究所,安徽合肥230001

出　　处：《中国神经肿瘤杂志》2010年第1期19-25,共7页Chinese Journal of Neuro-Oncology

基　　金：国家自然科学基金项目(No.30672166)

摘　　要：背景与目的:瘤周微环境对胶质瘤干细胞起着重要作用。本研究检测CD133、Nestin、CD31和PCNA在脑肿瘤干细胞壁龛中的表达,探讨脑肿瘤干细胞生存的微环境——壁龛的结构、分布及其内部细胞的增殖潜能。方法:(1)采用免疫组织化学SP法检测CD133、Nestin和PCNA在65例胶质瘤组织中的表达。(2)采用免疫荧光双染法检测CD133/CD31、CD133/PCNA、CD133/Nestin、Nestin/CD31和Nestin/PCNA的共表达情况,计算CD133+壁龛、CD133+血管、PCNA+细胞、Nestin+壁龛和Nestin+血管所占的百分率,并将壁龛的表达率和壁龛内PCNA+细胞百分率与肿瘤病理分级进行相关性分析。结果:按照WHO2007年的神经系统肿瘤分类分级标准所有标本分为Ⅱ级22例,Ⅲ级23例,Ⅳ级20例,随着肿瘤级别的升高,CD133+壁龛的百分比越来越高(P=0.000),并且与CD133+血管之间呈正相关(r=0.549,P=0.001);同样Nestin+壁龛的百分比也越来越高(P=0.000),并且与Nestin+血管之间呈正相关(r=0.388,P=0.018);同时;对壁龛内PCNA+细胞百分比进行统计学分析,发现随着肿瘤级别的升高,PCNA+细胞的百分比差异有显著性(F=44.782,P=0.000)。壁龛在各级别胶质瘤中均有表达,在低级别组中,壁龛阳性率较低,壁龛内增殖细胞较少,与相邻壁龛之间界限清晰,并且,周围血管分布较少。在高级别组中,壁龛阳性率高,壁龛之间无明显界限,壁龛内细胞增殖活跃,周围可见丰富的微血管分布。壁龛中除CD133+/Nestin+BTSC外,还可见CD133+/Nestin-细胞、CD133-/PCNA+细胞等亚群细胞。结论:CD133+壁龛和Nestin+壁龛随着肿瘤级别的升高其表达率明显增加,均围绕着微血管分布,并且微血管系统在维护BTSCs壁龛结构中起了非常重要的作用。BACKGROUND OBJECTIVE：Microenvironment around tumors plays an important role in the maintenance of glioma stem cells.The aim of the present study was to investigate the expression of CD133,Nestin,CD31 and proliferating cell nuclear marker（PCNA） in the brain tumor stem cell niche.METHOD：Samples included 22 low-grade（2007 WHO grade II） and 43 high-grade（2007 WHO grade III,IV） gliomas.（1） The expressions of Nestin,CD133 and PCNA were detected using immunohistochemistry.The percentage of the CD133 ＋ niches,CD133＋ blood vessels,Nestin＋ niches,PCNA＋ cells and Nestin＋ blood vessels was calculated.（2） Double immunofluorescence staining was used to detect the co-expression of CD133/CD31,CD133/PCNA,CD133/Nestin,Nestin/CD31 and Nestin/PCNA.The correlation of the two different marked niches with the corresponding positive vascular endothelial cells or gliomas＇ grading was determined.RESULT：Both the CD133＋ niches and Nestin ＋ niches were located perivascularly in all glioma tissues.In the lowgrade gliomas,the positive expression of the CD133＋ niches is low and with few proliferating cell in them.The boundary with the neighboring niches was clear,and there were few blood vessels distributed around the surroundings.While in the highgrade gliomas,the positive expression of the CD133＋ niches was high and with more proliferating cells in them.There was no obvious boundary of the neighboring niches.More blood vessels were observed to be distributed around the surroundings.In the niches,there were also subgroups of cells,such as CD133＋/Nestin-cells and CD133＋/PCNA-cells.There was positive correlation between the CD133＋ niches and CD133＋ blood vessels（r=0.549,P=0.001） which similar to the correlation between the Nestin＋ blood vessels and Nestin＋ niches（r=0.388,P=0.018）.With the increase of the tumor grade,both the CD133＋ niches（P=0.000）,Nestin＋ niches（P=0.000） and PCNA＋ cells（P=0.000） increased significantly.CONCLUSION：Our findings showed that either

关 键 词：胶质瘤 脑肿瘤干细胞 壁龛 免疫组化 

分 类 号：R739.41[医药卫生—肿瘤]