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 gast ric, 3 colonic and 8 pancreatic) gastrointestinal tumour cell lines were ex amined for the expression of CD46, CD55 and CD59 with respect to the regula tory 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 compa rable levels, whereas the basal expression of CD55 mRNA was heterogeneous. The complement inhibitor proteins were detected in all cell lines using spe cific antibodies. Additional immunohistochemical stainings of gastrointesti nal tissue specimens supported these findings. IFN-gamma evoked a weak indu ction 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 w as accompanied by a marked increase of the corresponding transcripts. We co nclude that membrane-bound complement inhibitors are broadly expressed in g astrointestinal tumour cells and vary in their susceptibility to IFN-gamma. Thus, they may be involved in tumour escape mechanisms in gastric, pancrea tic and colorectal cancer. (C) 1999 Elsevier Science Ltd. All rights reserv ed.