Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.
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DOI:
10.1371/journal.pone.0068187
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Sato N
Sato N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yasuda K;Torigoe T;Morita R;Kuroda T;Takahashi A;Matsuzaki J;Kochin V;Asanuma H;Hasegawa T;Saito T;Hirohashi Y;Sato N

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肿瘤干细胞样细胞(Cancer stem-样cells, CSCs)/癌起始细胞(Cancer - initiation cells, CICs)是一类具有自我更新能力、分化潜力和高肿瘤起始能力的肿瘤细胞。通过侧群体(SP)分析、ALDEFLUOR测定和细胞表面标记分离卵巢癌CSCs/CICs。然而,这些方法并不是CSCs/CICs的明确标记,有必要改进现有的方法来鉴定更高纯度的CSCs/CICs。本研究分析了卵巢癌细胞的SP细胞和醛脱氢亮(ALDHBr)细胞。SP细胞和ALDHBr细胞分别比主要群体(MP)细胞和ALDHLow细胞表现出更高的肿瘤启动能力和更高的干细胞标记物——性别决定区Y-box 2 (SOX2)的表达水平。我们分析了SP和ALDHBr重叠群体(SP/ALDHBr),发现SP/ALDHBr群体比SP细胞或ALDHBr细胞表现出更高的肿瘤启动能力,仅102个细胞就能启动肿瘤。SP/ADLHBr细胞比SP/ALDHLow、MP/ALDHBr和MP/ALDHLow细胞表现出更高的成球能力、顺铂抗性、脂肪细胞分化能力和SOX2表达。SOX2基因敲除抑制卵巢癌细胞的肿瘤起始。在几种妇科癌细胞中检测到SP/ALDHBr群体,HEC-1子宫内膜样腺癌细胞的比例为0.1%,MCAS卵巢粘液腺癌细胞的比例为1%。综上所述,利用SP和ALDHBr重叠群体分离高纯度CSCs/CICs是一种很有前途的方法,SOX2可能是卵巢CSCs/CICs的一种新的功能标记物。
Cancer stem-like cells (CSCs)/cancer-initiaiting cells (CICs) are defined as a small population of cancer cells that have self-renewal capacity, differentiation potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have been isolated by side population (SP) analysis, ALDEFLUOR assay and using cell surface markers. However, these approaches are not definitive markers for CSCs/CICs, and it is necessary to refine recent methods for identifying more highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde dehydrogenese bright (ALDHBr) cells from ovarian cancer cells. Both SP cells and ALDHBr cells exhibited higher tumor-initiating ability and higher expression level of a stem cell marker, sex determining region Y-box 2 (SOX2), than those of main population (MP) cells and ALDHLow cells, respectively. We analyzed an SP and ALDHBr overlapping population (SP/ALDHBr), and the SP/ALDHBr population exhibited higher tumor-initiating ability than that of SP cells or ALDHBr cells, enabling initiation of tumor with as few as 102 cells. Furthermore, SP/ADLHBr population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDHLow, MP/ALDHBr and MP/ALDHLow cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDHBr population was detected in several gynecological cancer cells with ratios of 0.1% for HEC—1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous adenocarcinoma cells. Taken together, use of the SP and ALDHBr overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.
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发表时间: 2009-06-26
期刊: Science (New York, N.Y.)
影响因子: --
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发表时间: 2007-06
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发表时间: 2012-01-01
期刊: Oncoimmunology
影响因子: 7.2
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发表时间: 2008-04-01
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