Distribution of CXCL12 and CXC chemokine receptor-4 in glioblastoma microenviroment and the role of them in invasion and migration

Abstract

Objective To detect the expression of CXCL12/CXC chemokine receptor-4 (CXCR4) in glioblastoma microenviroment and explore the role of CXCL12/CXCR4 in invasion and migration.Methods The surgically resected specimens were collected from the core of mass,junctional zones between tumor and peritumoral areas and peritumoral edematous areas in 45 patients with glioblastoma.Immunohistochemistry was employed to detect the expression of CXCL12,CXCR4 and matrix metalloproteinase (MMP)-9 in tissue specimens.Human glioma U251 cells were treated with CXCL12 and AMD3100 (CXCR4 inhibitor).The expression of MMP-9 in treated and control cells was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting.Results In the core of mass,junctional zones and peritumoral edematous areas,the scores of CXCL12 were 4.2 ± 1.3,2.8 ±0.8 and 1.6 ± 0.5,those of CXCR4 were 4.6 ± 0.9,3.0 ± 0.7 and 1.8 ± 0.8,and those of MMP-9 were 5.2 ±0.8,3.8 ±0.8 and 2.6 ±0.5,respectively.The expression of CXCL12,CXCR4 and MMP-9 showed significant difference in above different areas (P ＜ 0.05).The expression of CXCL12/CXCR4 and MMP-9 was positively correlated (CXCL12 and MMP-9 r =0.769,P ＜ 0.05,CXCR4 and MMP-9 r =0.948,P ＜0.05).The expression values of MMP-9 mRNA were 0.968 ±0.065,0.187 ±0.028 and 0.294 ±0.042 in CXCL12 treated,AMD3100 treated and control groups,and the expression values of MMP-9 protein were 0.605 ±0.011,0.358 ±0.009 and 0.449 ±0.026,respectively.There was significant difference among those groups (P ＜ 0.05).Conclusion CXCL12/CXCR4 may promote the invasion and migration of glioma cells via the upregulated expression of MMP-9.CXCR4 could be a potential target against the invasion and migration of glioblastoma. Key words: Chemokine ; Glioblastoma ; Microenviroment ; Invasion ; Migration