VEGF通过影响CXCR4的表达调节卵巢癌细胞侵袭性的研究  

VEGF promotes ovarian carcinoma invasion by regulating the expression of CXCR4

作　　者：汪春年[1] 吴晓英[2] 吕辉[2] 何向蕾[1] 

机构地区：[1]宁波市医疗中心李惠利医院病理科,315040 [2]中南大学湘雅医学院超微结构教研室

出　　处：《浙江医学》2010年第2期226-229,共4页Zhejiang Medical Journal

摘　　要：目的 初步探讨卵巢癌细胞中血管内皮生长因子（VEGF）是否通过影响趋化因子受体CXCR4的表达,从而调节癌细胞的侵袭性.方法 以卵巢癌Caov-3细胞系为研究对象,运用RT-PCR和流式细胞术检测VEGF因子对卵巢癌Caov-3细胞系中CXCR4 mRNA及其蛋白质表达水平的影响,同时采用Boyden侵袭小室检测VEGF因子刺激后Caov-3细胞侵袭性的变化;并应用免疫组化技术检测VEGF与CXCR4在卵巢癌组织中的表达情况.结果 PCR产物凝胶电泳结果 显示,VEGF因子可显著增加Caov-3细胞中CXCR4 mRNA的表达：流式细胞仪检测发现,VEGF因子刺激细胞24h后,细胞平均荧光强度为26.20±1.45,与对照组比较,差异有统计学意义（P〈0.01）;VEGF刺激细胞后癌细胞的侵袭性显著增强,加入中和抗体后,癌细胞的侵袭性呈剂量依赖式下降.免疫组化检测结果 提示：卵巢癌中VEGF表达水平在不同转移状况和腹水量间的差异均有统计学意义（均P〈0.01）;CXCR4的表达水平在不同临床分期和转移状况间的差异均有统计学意义（均P〈0.05或0.01）;卵巢癌组织中VEGF蛋白与CXCR4蛋白的表达呈正相关（Spearman相关系数为0.575,P〈0.01）.结论 VEGF因子可通过影响卵巢癌细胞中CXCR4分子的表达,从而增强肿瘤细胞的侵袭性,CXCR4中和抗体则可抑制这一效应;卵巢癌组织中,VEGF与CXCR4的表达均与转移有关,且两者的表达呈正相关.Objective To investigate the effect of VEGF on invasive activity of ovarian cancer cells through regulating CXCR4 expression. Methods Ovarian carcinoma Caov-3 cells were treated with vascular epithelial growth factor （VEGF）. The expression of CXCR4 mRNA in Caov-3 cells was detected by RT-PCR; cell surface expression of CXCR4 was measured by FACScan flow cytometer. In vitro invasive activity of Caov-3 toward SDF-1 was measured by Boyden chamber. The expressions of VEGF and CXCR4 proteins were measured by immunohistochemical technique in 31 cases of human epithelial ovarian carcinoma. Results With VEGF stimulation, the expression of CXCR4 mRNA was significantly higher than that of controls. FACS analysis showed that after stimulation with VEGF （50ng/ml） for 24 h the mean fluorescence intensity on Caov-3 was 26.20 4- 1.45 and significantly increased compared with controls （P〈0.01）. The invasive activity of stimulated cells was significantly increased compared with those of control cells. The neutralizing monoclonal CXCR4 antibody blocked the increase of invasion induced by VEGF in a dose-dependent manner. In patients with ovarian carcinoma the expression of VEGF was significantly associated with tumor metastasis and volume of ascites （P〈0.01）. The expression of CXCR4 in ovarian cancer was correlated significantly with clinical stages and tumor metastasis （P〈0.01 and 0.05）. The expression of VEGF was significantly correlated with the expression of CXCR4 （r =0.575,P〈0.01）. Conclusion VEGF can induce the expression of CXCR4 in Caov-3 cells, which in turn promotes invasive ability of cancer cells. There is significant correlation between VEGF and CXCR4 expression in ovarian cancer, and both might be involved in the metastasis of tumor.

关 键 词：卵巢癌 血管内皮生长因子 CXCR4 侵袭性 

分 类 号：R446.62[医药卫生—诊断学]