title: Incomplete radiofrequency ablation enhances invasiveness and metastasis of residual cancer of hepatocellular carcinoma cell HCCLM3 via activating β-catenin signaling.
abstract: BACKGROUND
  Radiofrequency ablation (RFA) is one of the curative therapies for hepatocellular carcinoma (HCC), however, accelerated progression of residual HCC after incomplete RFA has been reported more frequently. The underlying molecular mechanism of this phenomenon remains to be elucidated. In this study, we used an incomplete RFA orthotopic HCC nude mouse model to study the invasive and metastatic potential of residual cancer as well as the correlated mechanism.
  
  
  METHODS
  The incomplete RFA orthotopic nude mouse models were established using high metastatic potential HCC cell line HCCLM3 and low metastatic potential HCC cell line HepG2, respectively. The changes in cellular morphology, motility, metastasis and epithelial-mesenchymal transition (EMT), and HCC cell molecular markers after in vitro and in vivo incomplete RFA intervention were observed.
  
  
  RESULTS
  Pulmonary and intraperitoneal metastasis were observed in an in vivo study. The underlying pro-invasive mechanism of incomplete RFA appeared to be associated with promoting EMT, including down-regulation of E-cadherin and up-regulation of N-cadherin and vimentin. These results were in accordance with the in vitro response of HCC cells to heat intervention. Further studies demonstrated that β-catenin was a pivotal factor during this course and blocking β-catenin reduced metastasis and EMT phenotype changes in heat-treated HCCLM3 cells in vitro.
  
  
  CONCLUSIONS
  Incomplete RFA enhanced the invasive and metastatic potential of residual cancer, accompanying with EMT-like phenotype changes by activating β-catenin signaling in HCCLM3 cells.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Zong-Tao
authors.initials: ZT
authors.lastname: Chai
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, P. R. China.
authors.forename: Zi-Man
authors.initials: ZM
authors.lastname: Zhu
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhu
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: De-Ning
authors.initials: DN
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Qilu Hospital, Shandong University, Jinan, P. R. China.
authors.forename: Qiang-Bo
authors.initials: QB
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Zhao
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Ao
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Ren
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Gao
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, P. R. China.
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D056945:Hep G2 Cells; D006358:Hot Temperature; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D018365:Neoplasm, Residual / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051176:beta Catenin