title: CD59 expressed on a tumor cell surface modulates decay-accelerating factor expression and enhances tumor growth in a rat model of human neuroblastoma.
abstract: It has been hypothesized that complement inhibitors expressed on the surface of tumor cells prevent effective immune-mediated clearance. Whereas there are in vitro data to support this hypothesis, the species-selective activity of complement inhibitors has been a hindrance to investigating the role of membrane-bound complement inhibitors in rodent models of human cancer. The CD59-positive LAN-1 human neuroblastoma cell line was significantly more sensitive to lysis by rat complement than by human complement, illustrating the species selectivity of endogenously expressed complement inhibitors. Transfection of LAN-1 cells with rat CD59, an inhibitor of the terminal cytolytic membrane attack complex, effectively protected the cells from lysis by rat complement in vitro. When LAN-1 cells stably expressing rat CD59 were inoculated into immune-deficient rats, the onset of tumor growth and the rate of tumor growth were significantly enhanced compared with those of control-transfected LAN-1 cells. These data show directly that the expression of a complement inhibitor on a tumor cell promotes tumor growth. Flow cytometric analysis revealed that the endogenous expression of decay-accelerating factor (DAF), an inhibitor of complement activation, was up-regulated on the surface of cells after in vivo growth. Of further interest, higher levels of DAF were present on CD59-transfected cells than on control-transfected cells derived from tumors. Increased DAF expression correlated with decreased complement deposition on the tumor cell surface. These results show that expression of complement inhibitors on a tumor cell has functional consequences with regard to complement deposition in vivo and indicate that CD59 can indirectly effect complement activation and C3 deposition in vivo via a link between CD59 and DAF expression.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York 10016, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Caragine
authors.forename: N K
authors.initials: NK
authors.lastname: Cheung
authors.forename: S
authors.initials: S
authors.lastname: Tomlinson
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism*; D018957:CD59 Antigens / Q000096:biosynthesis*; D003165:Complement System Proteins / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000378:metabolism*; D051381:Rats; D011923:Rats, Nude; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D018076:DNA, Complementary; D003165:Complement System Proteins