CXCR4在胶质瘤诱导血管生成中的作用

Role of CXCR4 in human glioma angiogenesis

目的研究CXCR4在人脑胶质瘤中的表达及其与肿瘤恶性程度、微血管密度（MVD）之间的关系．进一步探讨CXCR4在胶质瘤血管生成中的作用及CXCR4作为抗肿瘤靶点的可能性。方法收集河南省人民医院神经外科自2009年9月至2011年9月手术切除的人脑胶质瘤标本41例，其中低度恶性胶质瘤（Ⅰ～Ⅱ级）18例，高度恶性胶质瘤（Ⅲ～Ⅳ级）23例。另外取行内减压术的脑外伤患者的新鲜脑组织10例作为对照。免疫组织化学染色检测标本CXCR4和CD34的表达，实时荧光定量PCR检测标本CXCR4 mRNA的表达。结果免疫组化染色结果显示对照组CXCR4表达阴性，脑胶质瘤组织CXCR4表达阳性28例（68．29％），脑胶质瘤组织MVD的表达高于对照组，且高度恶性胶质瘤组CXCR4表达阳性率、MVD的表达均高于低度恶性胶质瘤组，差异有统计学意义（P〈0．051；CXCR4表达阳性组MVD（42．51±6．99）明显高于CXCR4表达阴性组（25．98±4．99），差异有统计学意义（P〈0．05）；高度恶性胶质瘤组CXCR4mRNA的表达量（5．19±1．43）高于低度恶性胶质瘤组（2．28±0．71），差异有统计学意义（P〈0．05）。结论CXCR4在胶质瘤血管生成中发挥重要的作用．有可能成为胶质瘤抗血管生成治疗的新靶点。

Objective To investigate the relationships of CXCR4 expression with glioma malignancy and microvessel density （MVD） in human brain glioma tissues, and explore the role of CXCR4 in the process of glioma angiogenesis and the possibility of CXCR4 being target of antiangiogenic therapy. Methods Forty-one patients with brain gliomas, admitted to our hospital from September 2009 to September 2011, were chosen in our study; their glioma tissues （18 with low-grade malignant gliomas and 23 with high-grade malignant gliomas） and 10 normal brain tissues from patients with cerebral trauma were collected; immunohistochemistry was used to detect the CXCR4 and CD34 protein expressions; and real-time PCR was used to detect the CXCR4 mRNA expression. MVD was calculated through CD34 staining for microvessel endothelium. Results The CXCR4 expression was negative in controls, and positive in 28 brain glioma tissues （68.29%）; the MVD in the mierovessel endothelium of glioma tissues was significantly higher than that in the controls （P〈0.05）; CXCR4 expression and MVD were positively correlated with tumor malignant progress （P〈0.05）. The CXCR4 mRNA in high-grade glioma tissues （5.19±1.43） was obviously higher than that in low-grade glioma tissues （2.28±0.71, P〈0.05）. Conclusion CXCR4 might play a key role in human glioma angiogenesis and is a novel target for antiangiogenic therapy.