下调CXCR4表达对胶质瘤干细胞侵袭能力和VEGF分泌量的影响.docVIP

下调CXCR4表达胶质瘤干细胞侵袭能力和VEGF分泌量 赵林涛卞修武姜建勇王斌平轶芳余时沧　400038） 提要： 目的 观察胶质瘤干细胞CXCR4表达后对其侵袭能力和血管内皮生长因子（vascular endothelial growth factorVEGF）分泌量的影响。方法 胶质瘤干细胞标记物CD133和CXCR4共表达情况；分别从的U87细胞中培养出胶质瘤干细胞球，通过ranswell小室比较两者的侵袭能力；采用酶联免疫吸附验（ELISA）两者细胞培养上清VEGF的含量。结果胶质瘤干细胞CXCR4表达后，胶质瘤干细胞的侵袭能力下降干扰组17±5.8个对照组71±8.7个，VEGF分泌减少干扰组690±24pg/ml，48h 1504±53pg/ml；对照组 850±25pg/ml，48h 2001±150pg/ml）。结论表达可抑制胶质瘤干细胞的侵袭和促血管生成能力，提示CXCR4可能对胶质瘤干细胞进行治疗的靶点。 胶质瘤干细胞；CXCR4；侵袭；VEGF；血管生成 R 739. 41　 文献标识码：A Downregulation of CXCR4 expression inhibits invasion and VEGF production of glioma stem cells ZHAO Lin-tao, BIAN Xiu-wu, JIANG Jian-yong, WANG Bin, PING Yi-fang, YU Shi-cang. （Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038,China） Abstract： Objective To observe the effects of CXCR4 downregulation on the invasion capacity and VEGF secretion of glioma stem cells (GSCs).Methods Coexpression of CXCR4 and CD133 in U87 cells and their xenografts grown in the brain of nude mice was detected by indirect immunofluorescence under laser scanning microscopy. Tumorspheres were isolated from control U87 cells and CXCR4-siRNA U87 cells. We investigated the expression of CD133, nestin and CXCR4 in tumorspheres by laser scanning microscopy. Effects of CXCR4 downregulation on invasion and VEGF production of GSCs were detected by transwell assay and ELISA respectively. Results CXCR4 and CD133 could coexpress in U87 cells and their xenografts. Downregulation of CXCR4 expression inhibits the invasion capacity （siRNA: 17±5.8/HPF, control: 71±8.7 /HPF）and VEGF secretion of GSCs（siRNA: 24h 690±24pg/ml 48h 1504±53pg/ml, control: 24h 850±25pg/ml 48h 2001±150pg/ml）. Conclusions GSCs could express CXCR4 and downregulation of CXCR4 expression attenuates the invasion and pro-angiogenic capacity of GSCs, which suggests that targeting CXCR4 expressed on GSCs may be of benefit in glioma patients. key words: Glioma stem cells；CXCR4；Invasion；VEGF；Angiogenesis目前研究认为，肿瘤干细胞可以自我更新、多向分化