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

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?

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

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 correlation (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.