High expression of the antigen recognized by the monoclonal antibody GB24 on human breast carcinomas: a preventive mechanism of malignant tumor cells against complement attack?
GB24 is a mouse monoclonal antibody raised against a common trophoblast-lymphocyte cross-reactive antigen. GB24 detects the membrane cofactor protein (MCP, CD46), a member of the complement regulatory protein family, which serves as a cofactor for factor 1 mediated cleavage of C3b. This study investigated the reactivity of GB24 on 38 breast carcinomas and 34 normal/benign breast tissues by immunochemistry as well as the reactivity of F2B7-2, an antibody specific to the decay accelerating factor (DAF, CD55) of the complement. GB24 staining was present on both normal tissue and benign lesions, but very strong diffuse reactivity was observed on carcinomas. This reactivity increased with the tumor grade. By contrast, malignant tumor cells lacked DAF expression. F2B7-2 antibody reacted weakly with benign epithelial cells. Results were studied by computer assisted image analysis to accurately define the mean optical densities. The densitometric analysis of MCP positive carcinomas showed a high intensity of the staining. Expression of MCP and DAF on MCF-7 cell lines was analyzed by flow cytometry. MCF-7 cell lines were strongly stained by mAb GB24 only. These data suggest that selectively enhanced expression of the antigen recognized by GB24 is associated with malignant breast disorders. This high expression, which may reflect a protective mechanism by which tumor cells survive complement activation, may prove useful as a marker of malignant transformation.
Hofman
P
P
INSERM U364, University of Nice, France.
Hsi
B L
BL
Manie
S
S
Fenichel
P
P
Thyss
A
A
Rossi
B
B
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000276:immunology*; D001940:Breast / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D018958:CD55 Antigens; D018270:Carcinoma, Ductal, Breast / Q000276:immunology / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000276:immunology / Q000473:pathology; D018275:Carcinoma, Lobular / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D003165:Complement System Proteins / Q000276:immunology*; D003429:Cross Reactions; D004848:Epithelium / Q000276:immunology; D005260:Female; D018226:Fibroadenoma / Q000276:immunology / Q000473:pathology; D005348:Fibrocystic Breast Disease / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D014327:Trophoblasts / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497857:CD46 protein, human; D018958:CD55 Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D003165:Complement System Proteins