Preferential expression of chemokine receptor CXCR4 by highly malignant human gliomas and its association with poor patient survival
Preferential expression of chemokine receptor CXCR4 by highly malignant human gliomas and its association with poor patient survival
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高度恶性的人神经胶质瘤优先表达趋化因子受体CXCR4及其与患者生存率低的关系
DOI：
10.1227/01.neu.0000290905.53685.a2
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发表时间：
2007-09-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Ji Ming
中科院分区：
文献类型：
--
作者：
Bian, Xiu-Wu;Yang, Shi-Xin;Wang, Ji Ming
目的：CXCR 4参与恶性肿瘤的生长、转移和血管生成。方法：采用逆转录聚合酶链反应（RT-PCR）和免疫细胞化学方法检测人脑胶质瘤细胞系CXCR 4 mRNA和蛋白的表达。测量CXCR 4配体SDF-1 β诱导的肿瘤细胞趋化性和血管内皮生长因子的产生。异种移植模型用于评价胶质瘤细胞肿瘤发生。评估异种移植肿瘤和原发性人胶质瘤标本的CXCR 4表达的CXCR 4蛋白表达。分析CXCR 4表达与患者生存期的关系。结果：CXCR 4的表达与人脑胶质瘤细胞系和原发肿瘤的恶性程度直接相关，而CXCR 4的表达则与人脑胶质瘤细胞系和原发肿瘤的恶性程度直接相关。CXCR 4的激活诱导肿瘤细胞的趋化性和增加血管内皮生长因子的产生。表达较高水平CXCR 4的胶质瘤细胞在裸鼠中形成更快速生长和致死的肿瘤。表达CXCR 4的原发性人脑胶质瘤标本含有高密度微血管。CXCR 4阳性胶质瘤患者术后预后较差。脂氧合酶抑制剂Nordy可抑制胶质瘤细胞系CXCR 4的表达，并降低其在裸鼠体内的成瘤性。结论：CXCR 4的表达水平与胶质瘤的恶性程度有关，可能与胶质瘤的快速生长有关。
OBJECTIVE: CXCR4 is implicated in the growth, metastasis, and angiogenesis of malignant tumors. We investigated the potential role of CXCR4 in human gliomas.METHODS: The expression of CXCR4 messenger ribonucleic acid and protein by human glioma cell lines was examined by reverse-transcriptase polymerase chain reaction and immunocytochemistry analysis. Tumor cell chemotaxis and production of vascular endothelial growth factor induced by the CXCR4 ligand SDF-1 beta were measured. Xenograft models were used for evaluation of glioma cell tumorigenesis. CXCR4 expression by xenografted tumors and primary human glioma specimens were evaluated for CXCR4 protein expression. The relationship between CXCR4 expression and patient survival was analyzed. A synthetic lipoxygenase inhibitor, Nordy, was tested for its effects on glioma cell expression and function of CXCR4, as well as on glioma cell tumorigenicity.RESULTS: CXCR4 expression correlated directly with the degree of malignancy of the human glioma cell lines and primary tumors. Activation of CXCR4 induced tumor cell chemotaxis and increased production of vascular endothelial growth factor. Glioma cells expressing higher levels of CXCR4 formed more rapidly growing and lethal tumors in nude mice. Primary human glioma specimens expressing CXCR4 contained high-density microvessels. Patients with CXCR4-positive gliomas had poorer prognosis after surgery. The lipoxygenase inhibitor Nordy diminished CXCR4 expression by glioma cell lines in vitro and reduced their tumorigenicity in nude mice.CONCLUSION: The level of CXCR4 expression seems to correlate with the degree of malignancy of human gliomas and may contribute to their rapid growth.