Toll-like receptor 4 signaling promotes epithelial-mesenchymal transition in human hepatocellular carcinoma induced by lipopolysaccharide

BMC Medicine

Research Article

Kai Sun¹  Ying-Ying Jing¹  Jing Hou¹  Li-Xin Wei¹  Xue Zhao¹  Rong Li¹  Lu Gao¹  Meng-Chao Wu¹  Zhi-Peng Han¹  Shan-Shan Zhang¹  Yan Liu¹  Qiu-Dong Zhao¹ 

[1] Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, PR, China;

关键词: Toll-like receptor 4;    Epithelial-mesenchymal transition;    Lipopolysaccharide;    Human hepatocellular carcinoma;   

DOI  :  10.1186/1741-7015-10-98

 received in 2012-02-15, accepted in 2012-08-31,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe endotoxin level in the portal and peripheral veins of hepatocellular carcinoma (HCC) patients is higher and lipopolysaccharide (LPS), a cell wall constituent of gram-negative bacteria, has been reported to inhibit tumor growth. However, in this study, we found that LPS-induced toll-like receptor 4 (TLR4) signaling was involved in tumor invasion and survival, and the molecular mechanism was investigated,MethodsFour HCC cell lines and a splenic vein metastasis of the nude mouse model were used to study the invasion ability of LPS-induced HCC cells and the epithelia-mesenchymal transition (EMT) in vitro and in vivo. A total of 106 clinical samples from HCC patients were used to evaluate TLR4 expression and analyze its association with clinicopathological characteristicsResultsThe invitro and in vivo experiments demonstrated that LPS could significantly enhance the invasive potential and induce EMT in HCC cells with TLR4 dependent. Further studies showed that LPS could directly activate nuclear factor kappa B (NF-κB) signaling through TLR4 in HCC cells. Interestingly, blocking NF-κB signaling significantly inhibited transcription factor Snail expression and thereby inhibited EMT occurrence. High expression of TLR4 in HCC tissues was strongly associated with both poor cancer-free survival and overall survival in patients.ConclusionsOur results indicate that TLR4 signaling is required for LPS-induced EMT, tumor cell invasion and metastasis, which provide molecular insights for LPS-related pathogenesis and a basis for developing new strategies against metastasis in HCC.

【 授权许可】

Unknown   
© Jing et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.