CXCL12-CXCR4轴促进胶质母细胞瘤前神经间质转化  

CXCL12-CXCR4 axis promotes proneural-mesenchymal transition in glioblastoma

作　　者：许学文 宋廉[1] 杨晓晓 石卉[1] 龚爱华[2] 王鸣[1] 张礼荣[1] XU Xue-wen;Song Lian;YANG Xiao-xiao;SHI Hui;GONG Ai-hua;WANG Ming;ZHANG Li-rong(Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001;School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013, China)

机构地区：[1]江苏大学附属医院影像科,江苏镇江212001 [2]江苏大学医学院,江苏镇江212013

出　　处：《江苏大学学报（医学版）》2020年第1期18-23,共6页Journal of Jiangsu University：Medicine Edition

基　　金：新疆生产建设兵团社会发展科技攻关与成果转化计划(2016AD005);镇江市科技创新资金资助项目(SH2017027,SH2018031);江苏大学学生科研立项项目(17A474)

摘　　要：目的:探讨CXC趋化因子配体12-CXC趋化因子受体4(CXC chemokine ligand 12-CXC chemokine receptor 4,CXCL12-CXCR4)轴对脑胶质母细胞瘤前神经间质转化的作用。方法:分析TCGA-GBM基因数据库中CXCR4 mRNA在不同胶质瘤分子分型肿瘤组织中的水平差异及其对肿瘤患者生存率的影响;人胶质瘤LN428、U87MG细胞经不同浓度CXCL12(0、20、40、60、80、100 ng/mL)及20μmol/L普乐沙福(选择性CXCR4拮抗剂)预处理48 h,免疫印迹实验检测细胞内OLIG2、E-钙黏蛋白、YKL-40、N-钙黏蛋白和波形蛋白表达水平;Transwell实验检测细胞迁移和侵袭能力,CCK8法和克隆形成实验检测肿瘤细胞增殖能力。结果:TCGA-GBM数据库分析结果显示,与健康者相比,胶质瘤患者CXCR4 mRNA表达显著增高,且与患者生存率呈负相关;间质型胶质母细胞瘤组织标本中CXCR4 mRNA水平显著高于前神经型胶质母细胞瘤(P均<0.05)。与对照组相比,CXCL12组细胞间质型相关蛋白YKL-40、N-钙黏蛋白、波形蛋白表达水平显著升高,而前神经型相关蛋白OLIG2、E-钙黏蛋白表达水平显著降低,人胶质瘤LN428、U87MG细胞迁移和侵袭能力、增殖能力显著增强(P均<0.05);给予普乐沙福处理后,与CXCL12组相比,人胶质瘤LN428、U87MG细胞迁移和侵袭能力、增殖能力显著降低,且间质型相关指标蛋白表达显著降低,前神经型相关指标蛋白表达显著升高(P均<0.05)。结论:CXCL12-CXCR4轴具有促进胶质母细胞瘤前神经间质转化,及迁移和侵袭、增殖的作用。Objective:To investigate the effect of CXC chemokine ligand 12-CXC chemokine receptor 4(CXCL12-CXCR4)axis on proneural-mesenchymal transition in glioblastoma.Methods:The difference of CXCR4 mRNA in glioma molecular subtyping tumor tissues and its effect on tumor patients′survival rate were analyzed based on data in the TCGA-GBM gene database;human glioma LN428 and U87MG cells were pretreated with different concentrations of CXCL12(0,20,40,60,80,100 ng/mL)and 20μmol/L plerixafor(selective CXCR4 antagonist)for 48 h,the expression levels of OLIG2,E-cadherin,YKL-40,N-cadherin and Vimentin were detected by Western blotting,the cell migration and invasion ability were detected by Transwell assay,the proliferation ability was detected by CCK8 assay and colony formation assay.Results:According to the data in the TCGA-GBM database,compared with normal group,the mRNA expressions of CXCR4 in glioma patients was significantly increased,and it was negatively correlated with the survival rate of patients.The mRNA expression level of CXCR4 in mesenchymal glioblastoma tissue samples was significantly higher than that in proneural glioblastoma(all P<0.05).Compared with control group,the expressions of mesenchymal-associated proteins YKL-40,N-cadherin and Vimentin were significantly increased in CXCL12 group,while the expressions of the proneural-related proteins OLIG2,E-cadherin were markedly decreased,migration and invasion ability and proliferative ability of glioma LN428 and U87MG cells were greatly enhanced(all P<0.05).After treatment with plerixafor,migration and invasion ability and proliferative ability of glioma LN428 and U87MG cells were remarkably inhibited,expression of mesenchymal-related proteins was highly decreased,and expression of proneural-related proteins was increased(all P<0.05).Conclusion:The CXCL12-CXCR4 axis promotes proneural-mesenchymal transition,migration,invasion and proliferation of glioblastoma.

关 键 词：胶质瘤 CXCL12-CXCR4轴 分子分型 前神经间质转化 

分 类 号：R393[医药卫生—基础医学]