DEACETYLASE ACTIVITY OF HUMAN TUMOR-CELLS PRODUCING IMMUNOSUPPRESSIVEAMINOSUGARS - ITS POSSIBLE ROLE IN RESISTANCE TO CELL-MEDIATED CYTOTOXICITY

In the present study, we examined the presence of deacetylases capable of producing free hexosamines, which we have shown earlier to be immu nosuppressive against human natural killer (NK) cell-mediated cytotoxi city, from N-acetylhexosamines in human tumor cells. When human NK-res istant colon cancer cells (Colo-320DM) were incubated with acetyl-D-[1 ,6-H-3(N)]glucosamine, a significant conversion to [H-3]glucosamine oc curred. Deacetylation was demonstrated as a change of the substrate ra dioactivity into free glucosamine trapped by a cation exchange resin, and this was subsequently confirmed by paper chromatography. This deac etylase activity was detected in other NK-resistant tumor cell lines, especially in freshly isolated human renal and breast cancer cells and testicular seminoma cells. However, no deacetylase activity was detec ted in NK-sensitive target cells such as K562, MOLT-4, or HL-60 cells. The ability to produce free hexosamines from N-acetylated aminosugars may provide a new mechanism for the escape of tumor cells from the at tack of immune effector cells such as NK cells.