Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125
Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125
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DOI：
10.1016/j.ygyno.2005.07.030
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发表时间：
2005-12-01
影响因子：
4.7
通讯作者：
Clark, GF
中科院分区：
文献类型：
--
作者：
Patankar, MS;Jing, Y;Clark, GF
目标。CA125表达特异性寡糖，可以抑制人类自然杀伤（NK）细胞的细胞毒性。目前的研究是为了确定CA125调节NK细胞介导的细胞毒性的能力。从OVCAR-3细胞中分离到CA125，采用ELISA和超灵敏质谱法测定其纯度。用CA125处理外周血NK细胞，以cr -51标记的K562细胞为靶标进行标准细胞毒性试验。流式细胞术和Western blot检测NK细胞表面和细胞内标记物的表达。NK细胞与CA125共孵育72年，K562靶细胞的裂解率下降了50-70%。CA125孵育4个小时和24小时对nk介导的细胞溶解没有影响。在CA125浓度（10,000-100,000 U/ml）下观察到NK功能的抑制作用，预计该浓度明显低于肿瘤微环境中观察到的水平。与IL-2共刺激不能消除CA125的NK抑制反应。CA125不降低NK细胞的增殖或诱导凋亡，也不改变p561ck、磷脂酶c - γ 1、ZAP70或CD3 zeta的表达。然而，CA125确实诱导CD16的主要下调和CD94/ nkg2a的轻微表达降低。我们正在进行的研究和其他实验室最近的工作强调了这种粘蛋白的潜在生理作用。根据这里提供的数据，肿瘤来源的CA125很可能作为针对卵巢肿瘤的免疫反应的抑制因子。(c) 2005爱思唯尔公司版权所有。
Objectives. CA125 expresses specific oligosaccharides that can inhibit the cytotoxicity of human natural killer (NK) cells. The current study was undertaken to determine the ability of CA125 to modulate NK cell-mediated cytotoxicity.Methods. CA125 was isolated from OVCAR-3 cells and its purity was determined by ELISA and ultra-sensitive mass spectrometric analysis. Peripheral blood-derived NK were treated with CA125 and standard cytotoxicity assays were performed using Cr-51-labeled K562 cells as targets. The expression of cell surface and intracellular markers on NK cells was determined by either flow cytometry or Western blot analysis.Results. NK cells incubated with CA125 for 72 It exhibited a 50-70% decrease in the lysis of K562 targets. Incubation with CA125 for 4 It and 24 h had no effect on NK-mediated cytolysis. Inhibition of NK function was observed at CA125 concentrations (10,000-100,000 U/ml) that are expected to be significantly lower than those observed in the tumor microenvironment. Co-stimulation with IL-2 did not abrogate the NK inhibitory response of CA125. CA125 did not reduce proliferation or induce apoptosis of NK cells and alter the expression of p561ck, phospholipase C-gamma 1, ZAP70, or CD3 zeta. CA125 did, however, induce major downregulation of CD16 and minor decrease in expression of CD94/NKG2A.Conclusions. Our ongoing research and recent work performed by other laboratories highlights the potential physiologic role of this mucin. Based on the data presented here, it is likely that the tumor-derived CA125 acts as a suppressor of the immune response that is directed against the ovarian tumors. (c) 2005 Elsevier Inc. All rights reserved.