Alpha-fetoprotein triggers hepatoma cells escaping from immune surveillance through altering the expression of Fas/FasL and tumor necrosis factor related apoptosis-inducing ligand and its receptor of lymphocytes and liver cancer cells.
OBJECTIVE
To investigate the mechanism of alpha-fetoprotein (AFP) in escaping from the host immune surveillance of hepatocellular carcinoma.


METHODS
AFP purified from human umbilical blood was administrated into the cultured human lymphoma Jurkat T cell line or hepatoma cell line, Bel7402 in vitro. The expression of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and its receptor (TRAILR) mRNA were analyzed by Northern blot and Western blot was used to detect the expression of Fas and Fas ligand (FasL) protein.


RESULTS
AFP (20 mg/L) could promote the expression of FasL and TRAIL, and inhibit the expression of Fas and TRAILR of Bel7402 cells. For Jurkat cell line, AFP could suppress the expression of FasL and TRAIL, and stimulate the expression of Fas and TRAILR. AFP also could synergize with Bel7402 cells to inhibit the expression of FasL protein and TRAIL mRNA in Jurkat cells. The monoclonal antibody against AFP (anti-AFP) could abolish these functions of AFP.


CONCLUSIONS
AFP is able to promote the expression of FasL and TRAIL in hepatoma cells and enhance the expression of Fas and TRAILR in lymphocytes. These could elicit the escape of hepatocellular carcinoma cells from the host's lymphocytes immune surveillance.
Li
Meng-Sen
MS
Department of Biochemistry, Hainan Medical College, Haikou, China. mengsenli@163.com
Ma
Qiu-Ling
QL
Chen
Qian
Q
Liu
Xin-Hua
XH
Li
Ping-Feng
PF
Du
Guo-Guang
GG
Li
Gang
G
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D008099:Liver / Q000276:immunology / Q000473:pathology; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000494:pharmacology*; D019014:fas Receptor / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D000509:alpha-Fetoproteins; D019014:fas Receptor