趋化因子受体4在神经胶质瘤中的表达及血管生成中的作用

A pilot study on the expression of CXCR4 in glioma and its effect on glioma angiogenesis

目的:探讨趋化因子受体4(chemokine receptor 4,CXCR4)在神经胶质瘤中的表达及在血管生成中的作用。方法:通过免疫组化法检测正常或神经胶质瘤患者的瘤体组织标本CXCR4、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,其结果做方差分析及相关性分析;采用ELISA观察CXCR4的配体基质细胞衍生因子-1(stromal derived factor-1,SDF-1)对U87胶质瘤细胞系VEGF分泌的影响;同时利用多种处理方式(对照组、SDF-1处理组、CXCR4拮抗剂AMD3100处理组、CXCR4 RNA干扰处理组)作用于U87后,取其条件培养上清与人脐静脉内皮细胞系(human umbilical vein endothelial cells,HUVECs)共培养,比较小管样结构(tubule-like structure,TLS)生成数量的变化。结果:神经胶质瘤中CXCR4、VEGF的表达量随着肿瘤恶性度的升高而增加,且二者呈线性正相关(P<0.01)。ELISA实验表明SDF-1可通过CXCR4促进VEGF的分泌(P<0.01)。成管实验提示CXCR4与胶质瘤血管生成相关。结论:CXCR4与神经胶质瘤恶性度相关,且其配体SDF-1可通过CXCR4影响VEGF的表达,将CXCR4拮抗或干扰明显影响胶质瘤血管增生,提示CXCR4可能为神经胶质瘤的治疗提供相应靶点和思路。

Objective：To explore the relationship between the SDF-1 / CXCR4 chemokine axis and VEGF in glioma angiogenesis.Methods： Immunohistochemistry was used to semi-quantitate the expression of CXCR4 and VEGF in human glioma.To characterize the effect of CXCR4 on VEGF,U87 and HUVECs cells were co-cultured with or without SDF-1,and the secretion of VEGF in the supernatant was detected by ELISA.With diverse treatments（control,SDF-1,CXCR4 antagonist AMD3100 and CXCR4 siRNA treated group） of U87,the supernatant was collected for HUVEC culture,and tubule-like structure（TLS） were counted.Results： The expression of CXCR4 and VEGF in glioma was increased with the malignancy of glioma,and the results showed a significantly positive cor relation（P 0.01）.Moreover,the ELISA data demonstrated that CXCR4 was correlated with VEGF secretion and tube-formation（P 0.01）.Conclusion：CXCR4 was potentially correlated with the degree of malignancy of glioma,and SDF-1 facilitates the secretion of VEGF via CXCR4.In addition,CXCR4 was involved in glioma vascular proliferation,which may function as a potential target for the development of therapeutic strategies.