趋化因子受体及配体在卵巢癌细胞迁移中的作用  

Effects of Chemokine Receptor and Its Ligand on Migration of Ovarian Cancer Cells

作　　者：李芳[1] 朱怀仕 韩志强[1] 陈刚[1] 高庆蕾[1] 贾平[1] 张阿丽[1] 奚玲[1] 徐茜[1] 廖国宁[1] 王世宣[1] 卢运萍[1] 马丁[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院妇产科,湖北武汉4300302 [2]山东省济宁市第一医院放射科,山东济宁272111

出　　处：《癌症》2005年第1期23-27,共5页Chinese Journal of Cancer

基　　金：国家杰出青年科学基金资助项目(No.30025017);国家973重大基础科学基金资助项目(No.2002CB513100)~~

摘　　要：背景与目的:研究表明许多肿瘤细胞表达趋化因子受体,与肿瘤细胞的迁移与转移有密切关系。本研究拟探讨趋化因子受体CXCR4[chemokine(C.X.C)receptor4]及配体CXCL12[chemokine(C.X.Cmotif)ligand12]在上皮性卵巢癌细胞中的表达及在肿瘤细胞迁移中的作用。方法:采用RT鄄PCR和Westernblot检测15例上皮性卵巢癌组织、卵巢癌细胞株CAOV3、血管内皮细胞株HUVEC和10例正常卵巢组织中CXCR4的表达以及卵巢癌患者腹膜后淋巴结组织和输卵管平滑肌组织中CXCL12的表达。ELISA检测15例上皮性卵巢癌患者腹水中趋化因子CXCL12的含量。以Boyden小室检测重组人CXCL12、上皮性卵巢癌癌性腹水对CAOV3和HUVEC细胞的趋化活性的影响。结果:(1)在上皮性卵巢癌组织、CAOV3及HUVEC细胞中,CXCR4在mRNA及蛋白水平的相对表达量分别为2.30±1.12、1.89±1.20、1.68±1.11及1.35±0.14、1.86±0.34、1.96±0.23,正常卵巢组织在mRNA及蛋白水平均未检测到CXCR4表达;(2)卵巢癌癌性腹水定量检查结果显示,CXCL12含量为632～9326pg/ml(中位数为6237pg/ml)。卵巢癌患者腹膜后淋巴结组织中,CXCL12mRNA表达量的平均值为1.14±0.87,卵巢癌患者输卵管平滑肌组织未检测出CXCL12表达;(3)重组人CXCL12可诱导CAOV3及HUVEC细胞的迁移,其趋化指数分别为3.BACKGROUND & OBJECTIVE: Chemokine receptors express on many tumor cells, and closely correlate with migration and metastasis of tumor cells. This study was to investigate expressions of chemokine(C-X-C) receptor 4 (CXCR4) and chemokine (C-X-C motif) ligand 12 (CXCL12) in human ovarian epithelial tumor cells, and their effects on migration of tumor cells. METHODS: Expression of CXCR4 mRNA and protein in 15 specimens of epithelial ovarian cancer tissue, ovarian cancer cell line CAOV3, endothelial cell line HUVEC, and 10 specimens of normal ovary tissue were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. Expression of CXCL12 mRNA in retroperitoneal lymph nodes, and smooth muscle of fallopian tube from the same 15 epithelial ovarian cancer patients was tested by RT-PCR, quantity of CXCL12 in ascites of 15 patients was assayed using ELISA. Boyden Transwells was used to analyze effects of CXCL12, and cancerous ascites on chemotaxis of CAOV3, and HUVEC cells. RESULTS: (1) Expression levels of CXCR4 mRNA in ovary cancer tissues, CAOV3 cells, and HUVEC cells were 2.30±1.12, 1.89±1.20, and 1.68±1.11, respectively; those of CXCR4 protein were 1.35±0.14, 1.86±0.34, and 1.96±0.23, respectively; CXCR4 mRNA and protein can't be detected in normal ovarian tissues. (2) In 15 ovarian cancer patients, concentrations of CXCL12 in ascites were 632-9 326 pg/ml, and CXCL12 mRNA level in retroperitoneal lymph nodes was 1.14±0.87, CXCL12 mRNA can't be detected in smooth muscle of fallopian tube. (3) Recombinant human CXCL12 induced migration of CAOV3, and HUVEC cells, the chemotactic indices (CI) were 3.9±1.2, and 4.1±1.6, significantly higher than those of control (1.0±0.4, and 1.1±0.7) (P<0.05); cancerous ascites induced migration of CAOV3 cells with CI of 1.9±0.8, significantly higher than that of control (P<0.05). CONCLUSION: CXCR4 and CXCL12 may play roles in metastasis of epithelial ovarian cancer by promoting migration of tumor cells and endothelial cells.

关 键 词：卵巢肿瘤 趋化因子 受体 细胞迁移 转移 

分 类 号：R737.31[医药卫生—肿瘤]