对荷人脑胶质瘤裸鼠血管生成模式的研究

The angiogenesis patterns of human glioma transplanted in nude mice

目的:探讨干细胞标志物ABCG2与肿瘤血管生成相关蛋白VEGF、CD34、VLA-2α在荷人脑胶质瘤裸小鼠移植瘤中的表达,同时运用CD34-PAS双染法观察移植瘤中的血供模式。方法:建立人脑胶质瘤裸小鼠皮下移植瘤模型30例。所有标本同时行HE染色和免疫组化检测,以正常人脑组织6例作为对照。光镜下检测上述基因的表达率和表达部位,并观察移植瘤中的血管生成模式。结果:ABCG2、VEGF、VLA-2α在移植瘤组织中阳性表达率均为100%,平均阳性细胞占有率分别为(3.93±1.438)%、(34.84±6.212)%、(30.33±4.428)%;CD34标记的微血管密度(MVD)计数平均达29.78±5.88个;内皮细胞被覆的血管、马赛克血管及拟态血管三种血供模式在移植瘤组织中均存在。结论:ABCG2高表达的细胞有亲血管分布趋向,VEGF、VLA-2α在移植瘤血管生成中起重要作用;恶性程度较高的移植瘤组织中存在着三种不同的血供模式。

Objective：To investigate the expression of molecular marker ABCG2 of stem cells and tumor angiogenesis-related gene products including vascular endothelial growth factor （VEGF）, CD34 and very late antigen alfa-2 （VLA-2α）in human gliomabearing nude mice and observe the patterns of angiogenesis in transplanted tumors by CD34-PAS double staining. Methods： The human glioma cells were subcutaneously transplanted in 30 nude mice. Six normal brain tissues were as controls. The hematoxylin and eosin staining and immunohistochemical examination were performed to determine the positive rate and the hot-spot of gene product expression. The patterns of angiogenesis were observed under light microscope. Results：The positive rates of ABCG2, VEGF, and VLA-2α expression were all 100% in transplanted tumors. The average percentage of positive cells was （ 3.93 ± 1. 438 ）% , （ 34. 84 ± 6. 212）%, （30.33 ± 4.428 ）%, respectively. The value of micro-vascular density （MVD） labeled by CD34 averaged at 29.78 ± 5.88. All the three microcirculation patterns, endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry, were present in xenografted human glioma tissue samples. Conclusions：The ABCG2-overexpressed cells tended to be located close to blood vessels. VEGF and VLA-2α play an important role in angiogenesis of transplanted tumors in nude mice. There exist three different microcirculation patterns in high malignant transplanted tumors.