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Incomplete radiofrequency ablation enhances invasiveness and metastasis of residual cancer of hepatocellular carcinoma cell HCCLM3 via activating ?-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 ?-catenin was a pivotal factor during this course and blocking ?-catenin reduced metastasis and EMT phenotype changes in heat-treated HCCLM3 cells in vitro.

Conclusion

Incomplete RFA enhanced the invasive and metastatic potential of residual cancer, accompanying with EMT-like phenotype changes by activating ?-catenin signaling in HCCLM3 cells.

SUBMITTER: Zhang N 

PROVIDER: S-EPMC4277411 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Incomplete radiofrequency ablation enhances invasiveness and metastasis of residual cancer of hepatocellular carcinoma cell HCCLM3 via activating β-catenin signaling.

Zhang Ning N   Wang Lu L   Chai Zong-Tao ZT   Zhu Zi-Man ZM   Zhu Xiao-Dong XD   Ma De-Ning DN   Zhang Qiang-Bo QB   Zhao Yi-Ming YM   Wang Miao M   Ao Jian-Yang JY   Ren Zheng-Gang ZG   Gao Dong-Mei DM   Sun Hui-Chuan HC   Tang Zhao-You ZY  

PloS one 20141226 12


<h4>Background</h4>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.<h4>Methods</h4>The in  ...[more]

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