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产生免疫抑制性氨基糖的人类肿瘤细胞的脱乙酰酶活性:其在对细胞介导的细胞毒性的抗性中的可能作用。

Deacetylase activity of human tumor cells producing immunosuppressive aminosugars: its possible role in resistance to cell-mediated cytotoxicity.

作者信息

Yagita M, Seppo A, Renkonen O, Saksela E

机构信息

Department of Internal Medicine, Tazuke-Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.

出版信息

Cancer Res. 1993 Dec 1;53(23):5600-4.

PMID:8242610
Abstract

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.

摘要

在本研究中,我们检测了人肿瘤细胞中能够从N - 乙酰己糖胺产生游离己糖胺的脱乙酰酶的存在情况,我们之前已表明这些游离己糖胺对人自然杀伤(NK)细胞介导的细胞毒性具有免疫抑制作用。当人NK抗性结肠癌细胞(Colo - 320DM)与乙酰 - D - [1,6 - ³H(N)]葡萄糖胺一起孵育时,会发生向[³H]葡萄糖胺的显著转化。脱乙酰作用表现为底物放射性转变为被阳离子交换树脂捕获的游离葡萄糖胺,随后通过纸层析法得以证实。在其他NK抗性肿瘤细胞系中检测到了这种脱乙酰酶活性,尤其是在新鲜分离的人肾癌细胞、乳腺癌细胞和睾丸精原细胞瘤细胞中。然而,在NK敏感的靶细胞如K562、MOLT - 4或HL - 60细胞中未检测到脱乙酰酶活性。从N - 乙酰化氨基糖产生游离己糖胺的能力可能为肿瘤细胞逃避诸如NK细胞等免疫效应细胞的攻击提供一种新机制。

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