Functional interaction between peritoneal mesothelial cells and stem cells of ovarian yolk sac tumor (SC-OYST) in peritoneal dissemination

Functional interaction between peritoneal mesothelial cells and stem cells of ovarian yolk sac tumor (SC-OYST) in peritoneal dissemination
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DOI:
10.1016/j.ygyno.2011.10.006
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发表时间:
2012-02-01
影响因子:
4.7
通讯作者:
Kikkawa, Fumitaka
Kikkawa, Fumitaka
中科院分区:
医学2区
文献类型:
--
作者:
Mitsui, Hiroko;Shibata, Kiyosumi;Kikkawa, Fumitaka

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目标。近年来,有研究表明生态位在维持肿瘤干细胞(CSCs)中起着重要作用。我们基于腹膜间皮细胞有可能为SC-OYST提供生态位的假设,研究了腹膜间皮细胞与SC-OYST之间的相互作用。我们将NOY1细胞分为CD133阳性细胞和阴性细胞。用NOY1与腹膜间皮细胞共培养,比较CD133的表达、集落形成、迁移和侵袭能力。此外,我们评估了AMD3100,一种针对趋化因子受体(CXCR4)的中和抗体的抑制作用。然后,我们检测了AMD3100是否影响NOY1-CD133+细胞的体内致瘤性。当NOY1细胞与腹膜间皮细胞共培养时,观察到CD133的高表达。NOY1-CD133+细胞的克隆数是NOY1-CD133-细胞的2.4倍。而与腹膜间皮细胞共培养时,则为4.3倍。当NOY1细胞在上层培养,腹膜间皮细胞在下层培养时,NOY1-CD133+细胞表现出比NOY1-CD133-细胞更强的迁移和侵袭能力。在共培养体系中加入AMD3100可抑制NOY1-CD133+细胞的集落形成、迁移和侵袭。此外,AMD3100还能抑制NOY1-CD133+细胞的体内致瘤性。我们的数据表明,腹膜间皮细胞有可能为NOY1细胞提供一个利基环境。对SC-OYST利基的研究将有助于阐明治疗方法的重要靶点。(C)2011 Elsevier Inc.保留所有权利。
Objective. In recent years it has been indicated that ecological niches play important roles in the maintenance of cancer stem cells (CSCs). We investigated interactions between peritoneal mesothelial cells and SC-OYST based on the hypothesis that peritoneal mesothelial cells have the potential to provide one of the niches for SC-OYST.Methods. We divided NOY1cells into CD133-positive and -negative cells. Using the co-culture of NOY1 and peritoneal mesothelial cells, we compared the expression of CD133, colony formation, and the capacity for migration and invasion. In addition, we assessed the inhibitory effects of AMD3100, a neutralizing antibody against a chemokine receptor (CXCR4). Then, we examined whether AMD3100 affects the tumorigenicity of NOY1-CD133+ cells in vivo.Results. When NOY1 cells were co-cultured with peritoneal mesothelial cells, we observed the high-level expression of CD133. The number of colonies of NOY1-CD133+ cells was 2.4 times that of NOY1-CD133- cells. In contrast, on co-culture with peritoneal mesothelial cells, it was 4.3 times. When NOY1 cells were cultivated in the upper layer and peritoneal mesothelial cells were cultivated in the lower chamber, NOY1-CD133+ cells showed a greater capacity for migration and invasion than NOY1-CD133- cells. By adding AMD3100 to the co-culture systems, the colony formation, migration, and invasion of NOY1-CD133+ cells were inhibited. In addition, AMD3100 inhibited the tumorigenicity of NOY1-CD133+ cells in vivo.Conclusions. Our data suggest that peritoneal mesothelial cells have the potential to provide one of the niches for NOY1 cells. Investigation of the niches of SC-OYST will help elucidate important targets for therapeutic approaches. (C) 2011 Elsevier Inc. All rights reserved.