CD151通过上皮间质转化及干性相关通路调控非小细胞肺癌脑转移的机制研究  

CD151 inhibits brain metastasis of non-small cell lung cancer by regulating epithelial-mesenchymal transition and stemness pathways

作　　者：王帅[1] 张诗珩[1] 张志敏[1] 杨镇洲[1] WANG Shuai, ZHANG Shiheng, ZHANG Zhimin, YANG Zhenzhou(Cancer Center, Institute of Surgery Research, Third Affiliated Hospital, Army Medical University （Third Military Medical University） , Chongqing, 400042, China)

机构地区：[1]陆军军医大学(第三军医大学)第三附属医院(野战外科研究所)肿瘤中心,重庆400042

出　　处：《第三军医大学学报》2018年第10期862-867,共6页Journal of Third Military Medical University

基　　金：重庆市基础科学与前沿技术研究重点项目(CSTC2015jcyjBX0084)~~

摘　　要：目的探讨四跨膜蛋白CD151在肺癌脑转移中的预测作用及相关分子通路机制。方法收集2010年12月至2015年6月本中心160例非小细胞肺癌(non-small cell lung cancer,NSCLC)患者临床资料,其中脑转移患者88例,无脑转移患者72例,采用免疫组织化学方法检测CD151在肺癌组织的表达,并运用Spearman分析CD151表达与脑转移相关性。再选择人NSCLC细胞株HCC827,应用siRNA干扰、Western blot、划痕和Transwell实验检测敲低CD151表达对细胞增殖、迁移状况以及上皮间质转化(EMT)、干性通路相关蛋白表达的影响。结果相对于无脑转移患者,NSCLC脑转移患者肺癌组织CD151表达显著增加(P=0.012),Spearman分析表明CD151高表达与脑转移呈正相关(r=0.478,P=0.004)。通过siRNA敲低CD151可上调Ecadherin表达,并下调Vimentin、SOX2、CD44和CD133表达,同时降低HCC827细胞增殖(P=0.026)与迁移能力(P=0.032)。结论 CD151可能通过调控EMT、干性通路相关蛋白表达影响NSCLC细胞的增殖、迁移,CD151可能是NSCLC脑转移的潜在预测因子。Objective To investigate the value of CD151 for predicting brain metastasis of lung cancer and explore its role in promoting lung cancer metastasis and the associated signaling pathways.Methods A total of 160 patients with non-small cell lung cancer（NSCLC） admitted in our center between December,2010 and June,2015 were enrolled in this study,including 88 patients with and 72 without brain metastases. CD151 expression in the lung cancer tissues was examined using immunohistochemistry and its correlation with brain metastasis was analyzed. In the in vitro experiment with human NSCLC cell line（HCC827 cells）,RNA interference technique,scratch-wound assay,Transwell assay and Western blotting were used to clarify the role of CD151 in regulating cell proliferation,migration,epithelial-mesenchymal transition,and expressions of proteins in the stemness pathways. Results Compared with those without brain metastasis,the patients with brain metastasis of NSCLC showed significantly up-regulated CD151 expression in the lung cancer tissues（P = 0. 012）. Spearman correlation analysis showed that a high expression of CD151 was positively correlated with brain metastasis of NSCLC（r = 0. 478,P = 0. 004）. HCC827 cells with CD151 knockdown mediated by a small interfering RNA showed obviously suppressed cell proliferation（P = 0. 026）and metastasis（P = 0. 032）, up-regulated expression of E-cadherin and down-regulated expression of vimentin,SOX2,CD44 and CD133. Conclusion CD151 promotes the proliferation and migration of NSCLC cells possibly by regulating the protein expression associated with epithelial-mesenchymal transition and stemness pathways,suggesting its value as a potential biomarker for predicting brain metastases of lung cancer.

关 键 词：CD151 非小细胞肺癌 脑转移 预测因子 

分 类 号：R730.23[医药卫生—肿瘤] R734.2[医药卫生—临床医学]