Tumor progression in vitro: the paradoxical natural antibody and complement-selected phenotype.
An in vitro model of tumor progression was employed to investigate the contribution of natural antibody (NAb) to antitumor resistance in vivo. Repeated cycles of L5178Y-F9 and SL2-5 tumor growth in the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) followed by the selective elimination of sensitive variants through complement-dependent syngeneic NAb lysis yielded tumors with a reduced sensitivity to NAb and complement, natural killer (NK) cells and the rapid elimination assay of natural resistance (NR). A dissection of the resistant phenotype revealed a reduction in the binding capacity of complement-fixing NAb and NK cells, a reduced susceptibility to hypotonic lysis and, paradoxically, increased fluorescence-detected NAb binding that correlated inversely with a reduced tumor frequency of threshold subcutaneous tumor inocula. The data distinguish tumor binding of NAb that leads to complement activation from other NAb binding and expose a difference between NR measured as the tumor frequency of threshold tumor inocula versus the rapid radiolabelled tumor elimination assay. Complement-dependent NAb lysis may not contribute significantly to the defense against small tumor foci; however, NAb-mediated processes associated with high fluorescence-detected NAb binding likely provide resistance.
Chow
D A
DA
Department of Immunology, Medical Faculty, University of Manitoba, Winnipeg, Canada.
Chan
J
J
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D003167:Complement Activation; D003602:Cytotoxicity, Immunologic; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007157:Immunologic Surveillance; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000912:Antibodies, Neoplasm; D007132:Immunoglobulin Isotypes; D013755:Tetradecanoylphorbol Acetate