Endometrial Cancer Side-Population Cells Show Prominent Migration and Have a Potential to Differentiate into the Mesenchymal Cell Lineage
Endometrial Cancer Side-Population Cells Show Prominent Migration and Have a Potential to Differentiate into the Mesenchymal Cell Lineage
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DOI：
10.2353/ajpath.2010.090056
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发表时间：
2010-01-01
影响因子：
6
通讯作者：
Wake, Norio
中科院分区：
文献类型：
--
作者：
Kato, Kiyoko;Takao, Tomoka;Wake, Norio
癌症干细胞样细胞亚群，被称为“侧群”（SP）细胞，已在几种肿瘤中发现，基于它们外排荧光染料Hoechst 33342的能力。虽然SP细胞已在正常人子宫内膜和子宫内膜癌中被发现，但对其特征知之甚少。在本研究中，我们从人子宫内膜癌细胞和大鼠子宫内膜细胞中分离并鉴定了表达致癌性人K-Ras蛋白的SP细胞。这些SP细胞表现为：(1)分化标志物表达水平降低；Ii)细胞培养物的长期增殖能力；Iii)体外自我更新能力；Iv)增强迁移、板足和尾足的形成；v)增强的致瘤性。SP细胞在裸鼠体内形成大的侵袭性肿瘤，由肿瘤细胞和细胞外基质丰富的基质样细胞组成。与非SP肿瘤相比，SP肿瘤中vimentin、α -平滑肌肌动蛋白和III型胶原蛋白的表达水平升高。此外，显微解剖样品分析和hec1 - sp -肿瘤的荧光原位杂交显示，细胞外基质富集的基质样细胞含有人DNA，证实基质样细胞来源于接种细胞。此外，在Matrigel实验中，SP细胞分化为α -平滑肌肌动蛋白表达细胞。这些发现表明SP细胞具有癌症干细胞样的特征，包括向间充质细胞谱系分化的潜力。（中华病理学杂志，2010,176:381-392;DOI: 10.2353/ajpath.2010.090056）
Cancer stem-like cell subpopulations, referred to as "side-population" (SP) cells, have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Although SP cells have been identified in the normal human endometrium and endometrial cancer, little is known about their characteristics. In this study, we isolated and characterized the SP cells in human endometrial cancer cells and in rat endometrial cells expressing oncogenic human K-Ras protein. These SP cells showed i) reduction in the expression levels of differentiation markers; ii) long-term proliferative capacity of the cell cultures; iii) self-renewal capacity in vitro; iv) enhancement of migration, lamellipodia, and uropodia formation; and v) enhanced tumorigenicity. In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor cells and stromal-like cells with enriched extracellular matrix. The expression levels of vimentin, alpha-smooth muscle actin, and collagen III were enhanced in SP tumors compared with the levels in non-SP tumors. In addition, analysis of microdissected samples and fluorescence in situ hybridization of Hec1-SP-tumors showed that the stromal-like cells with enriched extracellular matrix contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. Moreober, in a Matrigel assay, SP cells differentiated into alpha-smooth muscle actin-expressing cells. These findings demonstrate that SP cells have cancer stem-like cell features, including the potential to differentiate into the mesenchymal cell lineage. (Am J Pathol 2010, 176:381-392; DOI: 10.2353/ajpath.2010.090056)