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Down-regulation of β-centractin might be involved in dendritic cells dysfunction and subsequent hepatocellular carcinoma immune escape: a proteomic study

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Abstract

Aims

Proteomic study was used to clarify the mechanism of hepatocellular carcinoma (HCC) immune escape concerning Dendritic cells (DCs’) dysfunction and their association with HCC invasion.

Methods

Human peripheral blood mononuclear cells (PBMCs) derived DCs from healthy donors were pulsed with soluble cell lysates prepared from different metastatic potential human HCC cell lines. The total protein of these DCs was analyzed by two-dimensional electrophoresis and Electro-Spray Mass Spectrometry. The allostimulatoy capacity and phenotype of these DCs were also evaluated. The clinical significance of β-centractin, one of the largest quantitative changed spot, down-regulation in DCs was further evaluated in autologous PBMCs derived DCs pulsed with auto-tumor lysates in 26 HCC patients.

Results

The expression of β-centractin was found to be considerably lower either in DCs pulsed with HCCLM6 (high metastatic potential HCC cell line) lysates, accompanied by down-regulation of CD86 molecule and impaired allostimulatory capacity, than those of DCs pulsed with lysates from HCC cell lines with low or without metastatic potential or in DCs pulsed with lysates from HCC with invasiveness than those without invasiveness.

Conclusions

The down-regulation of β-centractin in DCs pulsed with high metastatic potential HCC lysates might associate with DCs dysfunction and HCC invasiveness.

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Abbreviations

HCC:

Hepatocellular carcinoma

DCs:

Dendritic cell

PBMCs:

Peripheral blood mononuclear cells

AFP:

Alpha-fetoprotein

APC:

Antigen presenting cell

TCR:

T-cell receptor

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 30200268). We thank Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences for helping with the Proteomic analysis, and Shanghai Fudan-Yueda Bio-Tech Co. Ltd., for helping with Western blot analysis of β-centractin expression.

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Authors and Affiliations

  1. Liver Cancer Institute and Zhong Shan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People’s Republic of China

    Yong-Qiang Weng, Shuang-Jian Qiu, Yin-Kun Liu, Jia Fan, Qiang Gao & Zhao-You Tang

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  1. Yong-Qiang Weng
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  2. Shuang-Jian Qiu
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  3. Yin-Kun Liu
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  4. Jia Fan
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  6. Zhao-You Tang
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Corresponding author

Correspondence to Zhao-You Tang.

Additional information

Yong-Qiang Weng and Shuang-Jian Qiu contributed equally to the work.

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Weng, YQ., Qiu, SJ., Liu, YK. et al. Down-regulation of β-centractin might be involved in dendritic cells dysfunction and subsequent hepatocellular carcinoma immune escape: a proteomic study. J Cancer Res Clin Oncol 134, 179–186 (2008). https://doi.org/10.1007/s00432-007-0267-0

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