CAJ | 학술논문

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(MMP-9)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)、Western blot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MMP-9的表达呈正相关(CXCL12与MMP-9比较,r=0.769、P＜0.01,CXCR4与MMP-9比较,r=0.948、P＜0.01).CXCL12处理组、AMD3100处理组及对照组U251细胞,在MMP-9mRNA水平上表达值依次为0.968±0.065、0.187±0.028、0.294±0.042,在MMP-9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MMP-9从而增强肿瘤细胞向外的侵袭、迁移,以CXCR4作为治疗靶点可以抑制胶质瘤细胞的侵袭与迁移.
목적 검측추화인자CXCL12급기수체CXC추화인자수체-4(CXCR4)재효질모세포류미배경중적표체,탐토기재종류침습、천이중적작용.방법 수집45례인효질모세포류조직표본,매례표본취류중심、종류여주위뇌조직교계구급류주수종구조직,채용면역조직화학방법검측상술조직중CXCL12、CXCR4급기질금속단백매-9(MMP-9)적표체.추화인자CXCL12화CXCR4억제제AMD3100처리인뇌효질류U251세포,채용역전록-취합매련반응(RT-PCR)、Western blot방법검측불동처리조U251세포MMP-9적표체.결과 재류중심、종류여주위뇌조직교계구급류주수종구조직,면역조직화학CXCL12표체분치의차위4.2±1.3、2.8±0.8、1.6±0.5,CXCR4표체분치의차위4.6±0.9、3.0±0.7、1.8±0.8,MMP-9표체분치의차위5.2±0.8、3.8±0.8、2.6 ±0.5,CXCL12、CXCR4급MMP-9재각구역간적표체차이균유통계학의의(P＜0.05)；불동구역조직중CXCL12/CXCR4화MMP-9적표체정정상관(CXCL12여MMP-9비교,r=0.769、P＜0.01,CXCR4여MMP-9비교,r=0.948、P＜0.01).CXCL12처리조、AMD3100처리조급대조조U251세포,재MMP-9mRNA수평상표체치의차위0.968±0.065、0.187±0.028、0.294±0.042,재MMP-9단백수평표체치의차위0.605 ±0.011、0.358±0.009、0.449±0.026,각처리조차이유통계학의의(P＜0.05).결론 CXCL12/CXCR4가이촉진종류세포분비MMP-9종이증강종류세포향외적침습、천이,이CXCR4작위치료파점가이억제효질류세포적침습여천이.
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.