Beta2-GPI: a novel factor in the development of hepatocellular carcinoma.
OBJECTIVE
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.
Jing
Xue
X
Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, People's Republic of China.
Piao
Yun-Feng
YF
Liu
Ye
Y
Gao
Pu-Jun
PJ
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006391:Hemangioma / Q000473:pathology / Q000601:surgery; D006498:Hepatectomy; D006509:Hepatitis B / Q000150:complications / Q000473:pathology / Q000601:surgery; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016328:NF-kappa B / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000235:genetics; D053482:beta 2-Glycoprotein I / Q000235:genetics* / Q000378:metabolism*
D006514:Hepatitis B Surface Antigens; D016328:NF-kappa B; D000509:alpha-Fetoproteins; D053482:beta 2-Glycoprotein I