CXCR4及NDRG1蛋白在前列腺癌中的表达及其与侵袭转移的相关性分析

目的 探讨趋化因子受体4(chemokine receptor 4, CXCR4)及N-myc下游调节基因1(N-myc downstream regulated gene 1, NDRG1)在前列腺癌组织及细胞系中的表达情况,明确其与前列腺癌恶性程度及转移的关系。 方法 应用免疫组织化学方法检测CXCR4蛋白在前列腺癌(46例)、良性前列腺增生(15例)及正常前列腺组织(10例)中的表达,分析其与前列腺癌病理分级及转移的关系。免疫印迹(Western blotting)法检测不同前列腺癌细胞系中CXCR4及磷酸化NDRG1(pNDRG1)表达差异。结果 免疫组织化学检测发现CXCR4蛋白在前列腺癌组织(30例)中过度表达,表达率为65.2%,其表达水平与前列腺癌病理分级及Gleason评分无显著相关性(P=0.081),而CXCR4蛋白表达与肿瘤转移密切相关,前列腺癌转移患者表达率明显高于无转移患者,差异有统计学意义(P=0.002)。Western blotting法检测在正常前列腺上皮细胞和不同前列腺癌细胞系中CXCR4及NDRG1蛋白表达不同,高转移潜能的去势抵抗前列腺癌细胞(PC3和DU145)中CXCR4表达较高,而作为转移抑制因子的pNDRG1表达则明显降低。结论 趋化因子受体CXCR4及转移抑制因子NDRG1可能参与调控前列腺癌的进展和转移,对前列腺癌的临床诊断和治疗有重要价值。

Expression of CXCR4 and NDRG1 and its association with invasion and metastasis in prostate cancer

Objective To investigate the expression and clinical significance of CXCR4 and N-myc downstream regulated gene 1 (NDRG1) in prostate cancer (PCa), and explore the relation between the protein expression and metastasis in PCa. Methods The expression of CXCR4 was detected by immunohistochemistry in 46 cases of PCa, 15 cases of benign prostatic hyperplasia (BPH) and 10 cases of normal prostate tissues (NP). The relation between the expression and clinicopathological changes was analyzed statistically. CXCR4 and phosphorylated NDRG1 (pNDRG1) were examined by Western blotting in prostate cancer cells. Results The expression level of CXCR4 in PCa was significantly higher than those in BPH and NP. The over-expression rate of CXCR4 in PCa was 65.2%. The expression of CXCR4 protein was not significantly associated with pathological grade and Gleason score (P=0.081). However, the increased expression of CXCR4 protein was significantly associated with the presence of metastasis of PCa (P=0.002). By Western blotting analysis, the expression of CXCR4 protein was stronger in PC3 and DU145 than in PrEC and LNCap cell lines. However, the expression of pNDRG1 decreased in the prostate cancer cells with high metastasis potential. Conclusion The expressions of CXCR4 and pNDRG1 are closely related to metastasis of PCa. CXCR4 and pNDRG1 have significant clinical implications for diagnosis and treatment of PCa.