骨桥蛋白诱导人胆囊癌细胞发生上皮-间充质转化促进转移复发  

Osteopontin-mediated gallbladder cancer cell epithelial-mesenchymal transition

作　　者：周闯[1] 李仁峰[1] 梁志伟[1] 赵龙栓[1] 翟文龙[1] 

机构地区：[1]郑州大学第一附属医院普通外科河南省肝胆胰疾病与器官移植学重点实验室,450052

出　　处：《中华实验外科杂志》2015年第5期1042-1044,共3页Chinese Journal of Experimental Surgery

基　　金：河南省科技厅科技攻关计划资助项目（132300410004）;郑州市科技局创新团队项目（131PCXTD617）

摘　　要：目的 探讨在人胆囊癌中骨桥蛋白（OPN）的临床意义及其促进转移复发的机制.方法 利用实时定量聚合酶链反应（Real-time PCR）技术分析OPN在15例胆囊癌及其对照组织中基因水平的表达;在人胆囊癌细胞株中通过细胞增殖、侵袭等功能实验分析OPN诱导胆囊癌细胞上皮-间充质转化（EMT）促进转移复发的具体机制.结果 OPN在人胆囊癌中较胆囊炎组织表达上调（P＜0.01）.克隆形成实验结果显示pWPI-OPN转染组细胞克隆形成数为（59.9±10.3）个,显著高于对照组的（23.7±9.2）个,差异有统计学意义（P＜0.05）.在体外实验显示慢病毒转染的OPN高表达胆囊癌细胞株GBC-SD发生EMT,其表现为间质化表型神经钙黏素（N-cadherin）和波形蛋白（Vimentin）上调和上皮化表型上皮钙黏素（E-cadherin）、紧密连接蛋白（ZO-1）的表达下调.同时,它能促进胆囊癌细胞运动和侵袭,过表达OPN组及对照组发生迁移的细胞数分别为[（369.3±23.4）、（84.7±18.7）个,P＜0.01].结论 OPN在胆囊癌组织中高表达与其进展有着直接的联系,其具体机制可能是通过诱导EMT促进胆囊癌的转移复发.Objective To investigate the association between osteopontin （OPN） and the epithelial-mesenchymal transition （EMT） in gallbladder cancer （GBC） and to elucidate the underlying signaling pathway.Methods We evaluated the clinical significance of OPN in 15 GBC patients using real-time quantitative polymerase chain reaction （Real-time PCR）.We also investigated the mechanisms of OPN mediating GBC EMT to promote metastasis in GBC cell lines in vitro.Results OPN was up-regulated in the human GBC tissues.The expression of OPN in human GBC tissues was significantly higher than in the cholecystitis tissues （P 〈 0.01）.Clone formation experiment results showed cell clone formation number （59.9 ± 10.3） in pWPI-OPN transfection group was significantly greater than that in control group （23.7 ± 9.2） （P 〈 0.05）.In vitro,the characteristics of EMT were induced by lentivirus transduction of OPN into GBC-SD cells,including the down-regulation of E-cadherin and ZO-1,and the concomitant up-regulation of N-cadherin and vimentin,whereas the ectopic expression of OPN in the GBC cell line promoted cell motility and invasiveness.The number of migrating cells in OPN over-expression group and control group was 369.3 ±23.4 and 84.7 ± 18.7 respectively （P 〈0.01）.The further functional studies revealed that OPN regulated the activation of ZEB1,which subsequently regulated EMT signaling pathway.Conclusion Our findings have uncovered a novel role for OPN in GBC metastasis,and provide potential therapeutic target for GBC therapy.

关 键 词：骨桥蛋白 胆囊癌 上皮-间充质转化 转移 

分 类 号：R735.8[医药卫生—肿瘤]