Characterisation of the complement-regulatory proteins decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46) on a human colonic adenocarcinoma cell line.
To avoid destruction by complement, normal and malignant cells express membrane glycoproteins that restrict complement activity. These include decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and protectin (CD59), which are all expressed on colonic adenocarcinoma cells in situ. In this study we have characterised the C3/C5 convertase regulators DAF and MCP on the human colonic adenocarcinoma cell line HT29. DAF was found to be a glycosyl-phosphatidylinositol-anchored 70-kDa glycoprotein. Blocking experiments with F(ab')2 fragments of the anti-DAF monoclonal antibody BRIC 216 showed that DAF modulates the degree of C3 deposition and mediates resistance to complement-mediated killing of the cells. The expression and function of DAF were enhanced by tumour necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta). Cells incubated with interferon gamma (IFN gamma) did not alter their DAF expression. Two MCP forms were expressed, with molecular masses of approximately 58 kDa and 68 kDa, the lower form predominating. MCP expression was up-regulated by IL-1 beta, but not by TNF alpha or INF gamma. Expression of DAF and MCP promotes resistance of colonic adenocarcinoma cells to complement-mediated damage, and represents a possible mechanism of tumour escape.
Bjørge
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Department of Microbiology and Immunology, Gade Institute, University of Bergen, Norway. line.bjorge@gades.uib.no
Jensen
T S
TS
Matre
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D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D018958:CD55 Antigens / Q000378:metabolism* / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins