Deacetylase activity of human tumor cells producing immunosuppressive aminosugars: 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 immunosuppressive against human natural killer (NK) cell-mediated cytotoxicity, from N-acetylhexosamines in human tumor cells. When human NK-resistant colon cancer cells (Colo-320DM) were incubated with acetyl-D-[1,6-3H(N)]glucosamine, a significant conversion to [3H]glucosamine occurred. Deacetylation was demonstrated as a change of the substrate radioactivity into free glucosamine trapped by a cation exchange resin, and this was subsequently confirmed by paper chromatography. This deacetylase 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 detected 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 attack of immune effector cells such as NK cells.
Yagita
M
M
Department of Internal Medicine, Tazuke-Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
Seppo
A
A
Renkonen
O
O
Saksela
E
E
D000117:Acetylglucosamine / Q000494:pharmacology; D000581:Amidohydrolases / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D006595:Hexosamines / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D009174:Mycoplasma / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology* / Q000276:immunology; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D006595:Hexosamines; D007166:Immunosuppressive Agents; D000581:Amidohydrolases; D000117:Acetylglucosamine