Expression and regulation by interferon-gamma of the membrane-bound complement regulators CD46 (MCP), CD55 (DAF) and CD59 in gastrointestinal tumours.
The membrane-bound complement inhibitors CD46 (membrane cofactor protein), CD55 (decay-accelerating factor) and CD59 (protectin) protect tumour cells against lysis by activated complement. In this study, a total of 14 (3 gastric, 3 colonic and 8 pancreatic) gastrointestinal tumour cell lines were examined for the expression of CD46, CD55 and CD59 with respect to the regulatory efficacy of interferon-gamma (IFN-gamma). The effects of IFN-gamma on mRNA and protein expression levels of CD46, CD55 and CD59 were evaluated by Northern blot hybridisation, RT-PCR, flow cytometry and immunostaining. In unstimulated cell lines, CD46 and CD59 transcripts were expressed at comparable levels, whereas the basal expression of CD55 mRNA was heterogeneous. The complement inhibitor proteins were detected in all cell lines using specific antibodies. Additional immunohistochemical stainings of gastrointestinal tissue specimens supported these findings. IFN-gamma evoked a weak induction of certain transcripts in a subset of the cell lines. Upregulation of protein expression was only observed in HT29 cells for CD55 and CD59 and was accompanied by a marked increase of the corresponding transcripts. We conclude that membrane-bound complement inhibitors are broadly expressed in gastrointestinal tumour cells and vary in their susceptibility to IFN-gamma. Thus, they may be involved in tumour escape mechanisms in gastric, pancreatic and colorectal cancer.
Schmitt
C A
CA
Department of Internal Medicine, Johannes-Gutenberg-University, Mainz, Germany.
Schwaeble
W
W
Wittig
B M
BM
Meyer zum Büschenfelde
K H
KH
Dippold
W G
WG
D015703:Antigens, CD / Q000378:metabolism*; D015152:Blotting, Northern; D015139:Blotting, Southern; D018958:CD55 Antigens / Q000378:metabolism*; D018957:CD59 Antigens / Q000378:metabolism*; D003169:Complement Inactivator Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D005770:Gastrointestinal Neoplasms / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D007371:Interferon-gamma