Induction of tumor cell resistance to macrophage-mediated lysis by phorbol esters: a postbinding event

Cellular Immunology
M Fishman, G Gunther

Abstract

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.

References

Jan 1, 1984·Annual Review of Immunology·D O Adams, T A Hamilton
Jan 1, 1980·Annual Review of Biochemistry·J A Badwey, M L Karnovsky
May 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·J J Sando, M C Young
Sep 1, 1982·The Journal of Experimental Medicine·R D SchreiberD H Katz

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