The complement regulatory proteins CD46 and CD59, but not CD55, are highly expressed by glandular epithelium of human breast and colorectal tumour tissues.
Three of the proteins protecting cells from autologous lysis by complement are: membrane cofactor protein (MCP; CD46), an inhibitor of the membrane attack complex formation (CD59), and decay accelerating factor (DAF; CD55). We have investigated the expression of these proteins in breast and colorectal carcinoma by immunohistochemistry and immunoblotting of breast tissue for CD46. CD46 was consistently and strongly expressed in the epithelial compartment in 26/28 ductal carcinomas of the breast, 9/9 fibroadenomas, and 9/11 cases of control non-neoplastic breast tissue. CD59 showed a similar degree of expression in the fibroadenomas (9/9), but was less strongly expressed in carcinomatous (22/28) and control (5/11) tissues. In marked contrast, no CD55 expression was detected in tissue from 15 ductal carcinomas. Immunoblotting of breast tissue for CD46 showed the same size of the molecule as for lymphocytes. It had however considerably stronger expression in tumour tissue than in non-neoplastic tissue. CD46 and CD59 were either lacking or only weakly expressed in the epithelial component of control colorectal mucosa: 2/15 and 5/15, respectively. In contrast, tissue samples from colorectal adenocarcinomas showed clear staining for both CD59 (10/18) and, more markedly, CD46 (15/18). There was no association between the pattern or intensity of CD46 and CD59 expression and tumour differentiation. As the complement regulatory proteins CD46 and CD59 are also strongly expressed by trophoblast at the feto-maternal tissue interface, these results support the concept that similar mechanisms are employed both by the genetically dissimilar fetus and certain tumours to evade immune attack by their host.
Thorsteinsson
L
L
Cancer Tissue Bank Research Centre, and Department of Immunology, University of Liverpool, England.
O'Dowd
G M
GM
Harrington
P M
PM
Johnson
P M
PM
D000230:Adenocarcinoma / Q000276:immunology; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis* / Q000097:blood; D015153:Blotting, Western; D001940:Breast / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology*; D018958:CD55 Antigens / Q000032:analysis*; D018957:CD59 Antigens / Q000032:analysis*; D018270:Carcinoma, Ductal, Breast / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology*; D003165:Complement System Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D018226:Fibroadenoma / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000097:blood; D008875:Middle Aged; D017154:Stromal Cells / Q000276:immunology
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D006680:HLA Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003165:Complement System Proteins