Induction of tumor cell resistance to macrophage-mediated lysis by phorbol esters: a postbinding event.
Activated macrophages can recognize, bind to, and lyse tumor cells in an antibody-independent manner. We have found that tumor cells pretreated with phorbol esters are markedly less susceptible to macrophage-mediated cytolysis, although the initial binding step is unaffected. Tumor cells preincubated with tumor-promoting phorbol esters (10(-8)-10(-6) M) were rendered resistant to macrophage kill whereas non-tumor-promoting derivatives were inactive in protecting tumor cells against cytolysis. Inhibition of [3H]phorbol-12,13-dibutyrate binding by other phorbol esters correlated with their potency as tumor promoters and their ability to render tumor cells resistant to macrophage killing. The role of protein kinase C as the receptor to phorbol esters was implicated by inhibition of PDBu binding by phenothiazine derivatives. This suggests a possible mechanism for the resistance of phorbol ester-treated tumor cells to macrophage-mediated cytolysis.
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D008223:Lymphoma / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D010703:Phorbol Esters / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011920:Rats, Inbred WF; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology; D013945:Thymoma / Q000276:immunology; D013953:Thymus Neoplasms / Q000276:immunology
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010703:Phorbol Esters; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate