胶质母细胞瘤微环境中CXCL12／CXC趋化因子受体4的表达分布及其在肿瘤侵袭迁移中的作用  

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

作　　者：陈聪[1] 刘志峰[1] 任炳成[1] 刘彬[1] 于圣平[1] 杨学军[1] 

机构地区：[1]天津医科大学总医院神经外科天津市神经病学研究所神经肿瘤实验室,300052

出　　处：《中华实验外科杂志》2013年第6期1271-1274,F0003,共5页Chinese Journal of Experimental Surgery

基　　金：基金项目：国家自然科学基金资助项目（81272782）

摘　　要：目的检测趋化因子CXCL12及其受体CXC趋化因子受体4（CXCR4）在胶质母细胞瘤微环境中的表达，探讨其在肿瘤侵袭、迁移中的作用。方法收集45例人胶质母细胞瘤组织标本，每例标本取瘤中心、肿瘤与周围脑组织交界区及瘤周水肿区组织，采用免疫组织化学方法检测上述组织中CXCL12、CXCR4及基质金属蛋白酶-9（MMPO）的表达。趋化因子CXCL12和CXCR4抑制剂AMD3100处理人脑胶质瘤U251细胞，采用逆转录-聚合酶链反应（RT-PCR）、Westernblot方法检测不同处理组U251细胞MMP-9的表达。结果在瘤中心、肿瘤与周围脑组织交界区及瘤周水肿区组织，免疫组织化学CXCL12表达分值依次为4．2±1．3、2．8±0．8、1．6±0．5，CXCR4表达分值依次为4．6±0．9、3．0±0．7、1．8±0．8，MMP．9表达分值依次为5．2±0．8、3．8±0．8、2．6±0．5，CXCL12、CXCR4及MMP-9在各区域间的表达差异均有统计学意义（P〈0．05）；不同区域组织中CXCL12／CXCR4和MMPO的表达呈正相关（CXCL12与MMPO比较，r=0．769、P〈0．01，CXCR4与MMPO比较，r=0．948、P〈0．01）。CXCL12处理组、AMD3100处理组及对照组U251细胞，在MMPOmRNA水平上表达值依次为0．968±0．065、0．187±0．028、0．294±0．042，在MMPO蛋白水平表达值依次为0．605±0．011、0．358±0．009、0．449±0．026，各处理组差异有统计学意义（P〈0．05）。结论CXCL12／CXCR4可以促进肿瘤细胞分泌MMPO从而增强肿瘤细胞向外的侵袭、迁移，以CXCR4作为治疗期点可以抑制膝后瘤细晌的停袭与讦移。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. Meth- ods 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. Immunohis- tochemistry 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 inva-sion and migration of glioblastoma.

关 键 词：趋化因子 胶质母细胞瘤 微环境 侵袭 迁移 

分 类 号：R73[医药卫生—肿瘤]