Phorbol ester tumor promoter regulation of natural antitumor antibody binding depends on protein kinase C and an intact microfilament system.
Phorbol ester tumor promoter treatment produced a biphasic effect on the binding of polyclonal whole-serum natural antibody (NAb) by L5178Y-F9 murine lymphoma cells. In vitro tumor growth in 100 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA) produced a rapid decrease followed by a reversible and unstable increase in NAb binding detected at 4 degrees C. The latter was associated with a functional decrease in NAb binding at 37 degrees C and increases in the tumorigenic and metastatic potentials in vivo. Colchicine, cytochalasin B and sodium azide inhibited the NAb binding of TPA-treated cells, while only colchicine reduced the binding of controls, suggesting the dependence of the TPA-induced increase in NAb binding on microfilament organization and active energy production. The non-tumor-promoting, non-PKC-activating TPA analogue 4-O-Me-TPA failed to alter NAb binding, arguing against nonspecific effects of TPA. The non-tumor-promoting, PKC-activating diacylglycerol, OAG, reproduced the initial decrease in NAb binding but was unable to mimic the subsequent TPA-induced increase. The PKC inhibitor H-7, but not HA1004, could block the TPA-induced increase in NAb binding. Together the data argue that PKC activation is required for both TPA-induced changes in NAb binding but that it is not sufficient to generate the energy- and microfilament-system-dependent, unstable high-NAb-binding phenotype associated with increased tumor progression.
Sandstrom
P A
PA
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Chow
D A
DA
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000187:drug effects* / Q000378:metabolism; D000915:Antibody Affinity / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D004075:Diglycerides; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate