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Beta2-GPI: a novel factor in the development of hepatocellular carcinoma

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Abstract

Purpose

This study investigated the effect and clinical significance of beta2-GPI in hepatocellular carcinoma (HCC).

Methods

Double fluorescent immunostaining analysis was performed in paraffin wax–embedded histological sections of nine HCC parenchyma, seven adjacent non-cancerous tissues and seven control liver tissues from hepatitis B virus (HBV) infected patients using a beta2-GPI polyclonal antibody and a HBV surface antibody. NF-κB activation was assessed by a non-radioactive electrophoretic mobility shift assay (EMSA) and immunofluorescence assay in SMMC-7721 HCC cells exposed to various treatments. The cells were transiently transfected with vectors expressing beta2-GPI (group one), HBsAg (group two), both beta2-GPI and HBsAg (group three), or with a control vector (group four). Untransfected cells (group five) were also used as a control. Alpha fetoprotein (AFP) expressions were also detected by ELISA in all groups.

Results

The highest degree of co-localization of beta2-GPI and HBsAg proteins was seen in the endochylema and occurred at the nuclear border in the cancer tissues. Weak beta2-GPI protein staining was present in the endochylema, with a strong signal for HBsAg protein in HBV control samples. Adjacent non-tumorous liver tissue samples also showed HBsAg staining but stronger beta2-GPI signals in the endochylema. In experiments with SMMC-7721 HCC cells, groups one and two had induced activation of NF-κB with the relative NF-κB DNA-binding activities of 55.84 and 51.12, respectively. However, the highest relative NF-κB DNA-binding activity was observed in group three (80.5). The percentages of cells with NF-κB translocated from the cytoplasm to nucleus in groups one, two, three, four and five compared with total cells were 13.5, 8.7, 24.9, 5.7 and 0.95%, respectively. The mean AFP levels were significantly higher in group three (0.0640 ± 0.0059) than in group five (P < 0.001). It appeared higher in group three than in group one (0.0562 ± 0.0060, P < 0.05) and group four (0.0585 ± 0.0040, P < 0.05), while no significant differences were seen between groups three and two, and between groups four and five.

Conclusions

Beta2-GPI may play a role in the development of HBV-related HCC by activating NF-κB via interaction of beta2-GPI and HBsAg.

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Abbreviations

Beta2-GPI:

Beta2-glycoprotein I

HCC:

Hepatocellular carcinoma

HBsAg:

Hepatitis B surface antigen

NF-κB:

Nuclear factor kappa-B

AFP:

Alpha fetoprotein

PBS:

Phosphate buffer saline

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Acknowledgments

We thank the Laboratory of Epidemiology, Veterinary Institute, Academy of Military Medical Sciences, People’s Republic of China. Written consent for publication was obtained from the patients or their relatives. This work was supported by the National Natural Science Foundation of China (No. 30070338).

Conflict of interest statement

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Hepatology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, People’s Republic of China

    Xue Jing, Yun-Feng Piao & Pu-Jun Gao

  2. Laboratory of Epidemiology, Veterinary Institute, Academy of Military Medical Sciences, Changchun, People’s Republic of China

    Ye Liu

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  1. Xue Jing
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  2. Yun-Feng Piao
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  3. Ye Liu
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  4. Pu-Jun Gao
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Correspondence to Pu-Jun Gao.

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Jing, X., Piao, YF., Liu, Y. et al. Beta2-GPI: a novel factor in the development of hepatocellular carcinoma. J Cancer Res Clin Oncol 136, 1671–1680 (2010). https://doi.org/10.1007/s00432-010-0825-8

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  • DOI: https://doi.org/10.1007/s00432-010-0825-8

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