XU Xue-wen1, Song Lian1, YANG Xiao-xiao1, SHI Hui1,GONG Ai-hua2, WANG Ming1, ZHANG Li-rong1
2020, 30(01): 18-23.
[Abstract]Objective: To investigate the effect of CXC chemokine ligand 12CXC chemokine receptor 4 (CXCL12CXCR4) axis on proneuralmesenchymal 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 TCGAGBM gene database; human glioma LN428 and U87MG cells were pretreated with different concentrations of CXCL12(0, 20, 40, 60, 80, 100 ng/mL) and 20 μmol/L plerixafor (selective CXCR4 antagonist) for 48 h, the expression levels of OLIG2, Ecadherin, YKL40, Ncadherin 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 TCGAGBM 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 mesenchymalassociated proteins YKL40, Ncadherin and Vimentin were significantly increased in CXCL12 group, while the expressions of the proneuralrelated proteins OLIG2, Ecadherin 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 mesenchymalrelated proteins was highly decreased, and expression of proneuralrelated proteins was increased (all P<0.05). Conclusion: The CXCL12CXCR4 axis promotes proneuralmesenchymal transition, migration, invasion and proliferation of glioblastoma.