Vimentin significantly promoted gallbladder carcinoma metastasis

作     者：DONG Ping HE Xiao-wei GU Jun WU Wen-guang LI Mao-lan YANG Jia-hua ZHANG Ling DING Qi-chen LU Jian-hua MU Jia-sheng CHEN Lei LI Song-gan DING Liang-fu WANG Jian-wei LIU Ying-bin 

作者机构：Department of General Surgery Xinhua Hospital affiliated toSchool of Medicine Shanghai Jiao Tong University Shanghai200092 China Department of General Surgery First Hospital Affiliated to JiaxingMedical School Jiaxing Zhejiang 314000 China Department of General Surgery Baozhen Hospital ChongmingShanghai 200092 China Department of Surgery Second Affiliated Hospital School ofMedicine Zhejiang University Hangzhou Zhejiang 310009China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2011年第000卷第24期

页      面：4236-4244页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：DONG Ping and HE Xiao-wei contributed equally to this work. This study was supported by grants from the National Natural Science Foundation of China (No. 30640060  30872502  30972918  81172026  81172029)  Natural Science Foundation of Zhejiang Province for Outstanding Young Researcher Groups (No. R2080452)  Foundation of Medical School  Shanghai Jiao Tong University (No. 09XJ21012) and Natural Science Foundation of Zhejiang Province (No. Y206860) 

主　　题：gallbladder neoplasm hepatic metastasis vimentin proteomics 

摘      要：Background The precise molecular mechanisms underlying the gallbladder carcinoma （GBC） metastasis has not been fully elucidated. Methods In the present study, metastasis-associated proteins were identified by comparative proteomic analysis. The functional study of the candidate protein vimentin was further investigated. First, a pair of higher and lower metastatic sublines （termed GBC-SD/M3 and GBC-SD, respectively）, originated from the same parental cell line, was screened by spontaneous tumorigenicity and metastasis in vivo in animal study and further characterized by metastatic phenotypes analysis in vitro. Subsequently, a proteomic approach comprised two-dimensional gel electrophoresis analysis and mass spectroscopy was used to identify and compare the protein expression patterns between higher metastatic GBC-SD/M3 and lower metastatic GBC-SD cell lines. Then twenty-six proteins were identified. Results Among the 26 proteins identified, fourteen proteins were up-regulated and 12 proteins were down-regulated in GBC-SD/M3. Vimentin was identified and found to be overexpressed in GBC-SD/M3 as compared with GBC-SD. This result was further confirmed by quantitative PCR and Western blotting analysis. Furthermore, the cell migration and invasion potency of GBC-SD/M3 in vitro was remarkably suppressed after small interference RNA-mediated knockdown of vimentin. Moreover, immunoblot and immunohistochemical analysis on 12 human GBC specimens showed consistently increased vimentin expression in metastases compared with primary tumors. Conclusion Tumor vimentin level may reflect the pathological progression in some GBC and may be a useful marker for predicting tumor metastasis and a therapeutic target for the treatment of GBC patients with metastases.