Decoy receptor 3 overexpression and immunologic tolerance in hepatocellular carcinoma (HCC) development.
The recently identified decoy receptor 3 (DcR3) inhibits FasL-induced apoptosis by binding to FasL, and it is considered to play a key role in the immune escape system of neoplastic cells. In order to examine the involvement of DcR3 in the immunologic tolerance of hepatocellular carcinoma (HCC), we investigated the amplification and expression of DcR3, FasL, and Fas in an HCC mice model using RT-PCR, western blotting, and ELISA, and analyzed the space-time relationship with various cytokines including the forkhead transcription factor forkhead/winged helix transcription factor gene (Foxp3), CTLA-4, TGF-beta, IL-10, TNF-alpha, and IFN-gamma. The RT-PCR results revealed that Fas expression preceded that of DcR3 during the early phases of tumorigenesis. Thereafter, the expression of DcR3 was up-regulated; however, the expression of Fas was down-regulated and eventually ceased. DcR3 and FasL were expressed and amplified simultaneously in muscle tumor. CTLA-4 expression was earlier than Foxp3, and both CTLA-4 and Foxp3 amplification and expression were consistent with that of DcR3. The results suggest that the elevated levels of DcR3, Foxp3, and CTLA-4 in tissue were positively correlated with tumor growth. The partial tumor immunoregulation inclined to negative modulation, and DcR3 may play an important role in inducing immunologic tolerance.
Chen
Caixia
C
Anti-Cancer Research Center, Xiamen University Medical College, XiaMen, China.
Zhang
Changgong
C
Zhuang
Guohong
G
Luo
Hongfang
H
Su
Jinhua
J
Yin
Pinh
P
Wang
Juan
J
D000199:Actins / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D060908:CTLA-4 Antigen; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D017931:DNA Primers; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D017931:DNA Primers; C505661:FASLG protein, human; C418974:FOXP3 protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D051858:Forkhead Transcription Factors; D053323:Receptors, Tumor Necrosis Factor, Member 6b