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The SDF-1/CXCR4 axis induces epithelial–mesenchymal transition in hepatocellular carcinoma

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Abstract

Hepatic stellate cells play a role in the migration process of hepatocellular carcinoma cells. Here, we address the role of the stromal-derived factor-1/CXC chemokine receptor 4 (SDF-1/CXCR4) axis on hepatocellular carcinoma progression. The expression of the SDF-1 and the CXCR4 was determined through western blotting and real-time PCR analysis using hepatic stellate (LX02) and hepatocellular carcinoma (MHCC97, SMMC7721, Hep3B, and HepG2) cell lines depleted of CXCR4 using shRNA. The migration of hepatocellular carcinoma cells following exogenous treatment with SDF-1 or in co-culture cell systems was measured using the Transwell assay. In parallel, the expression of epithelial–mesenchymal transition (EMT) markers was also determined. We found that SDF-1 is highly expressed in the hepatic stellate cell line LX02 and that the hepatocellular carcinoma cells express high levels of CXCR4. Co-culturing hepatocellular carcinoma cells with LX02 or exogenous treatment with SDF-1 induced an EMT as shown by increased migration. In contrast, ablation of CXCR4 expression in HepG2 cells attenuated the migration of HepG2 cells and suppressed the EMT. Thus, hepatic stellate cells can promote hepatocellular carcinoma cell invasion through the SDF-1/CXCR4 axis.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81201824) and by the Fundamental Research Funds for the Central Universities (No. XJTU-2013-01).

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Authors and Affiliations

  1. Department of General Surgery, First Affiliated Hospital Medical College of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Xuqi Li

  2. Department of Hepatobiliary Surgery, First Affiliated Hospital Medical College of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Pei Li, Qinhong Xu, Zheng Wu, Qingyong Ma & Zheng Wang

  3. Department of Gastroenterology, Fourth Hospital of Xi’an, Xi’an, 710004, Shaanxi, China

    Yuanhong Chang

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  1. Xuqi Li
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  2. Pei Li
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  5. Zheng Wu
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Corresponding author

Correspondence to Zheng Wang.

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Xuqi Li and Pei Li have contributed equally to this study.

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Li, X., Li, P., Chang, Y. et al. The SDF-1/CXCR4 axis induces epithelial–mesenchymal transition in hepatocellular carcinoma. Mol Cell Biochem 392, 77–84 (2014). https://doi.org/10.1007/s11010-014-2020-8

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  • DOI: https://doi.org/10.1007/s11010-014-2020-8

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