Cell surface Nestin is a biomarker for glioma stem cells
Cell surface Nestin is a biomarker for glioma stem cells
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DOI：
10.1016/j.bbrc.2013.03.021
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发表时间：
2013-04-19
影响因子：
3.1
通讯作者：
Kim, Hyunggee
中科院分区：
文献类型：
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作者：
Jin, Xiong;Jin, Xun;Kim, Hyunggee
肿瘤干细胞（cancer stem cells，CSCs）是恶性肿瘤中最具侵袭性的细胞类型。细胞表面蛋白通常用于分离和表征CSC。因此，鉴定CSC特异性细胞表面标志物对恶性肿瘤的诊断和治疗具有重要意义。我们发现，巢蛋白（VI型中间丝蛋白），像胶质瘤干细胞（GSC）标志物CD 133和CD 15，表现出不同水平的表达在原发性人类胶质母细胞瘤标本。与我们先前发现的细胞质巢蛋白在小鼠GSC中表达为细胞表面形式类似，巢蛋白的细胞表面形式在人GSC中也以不同水平表达。我们通过荧光激活细胞分选FACS分析从人GSC中分离细胞表面Nestin阳性细胞群，并观察到这些细胞群表现出强大的CSC特性，例如增加的肿瘤球形成能力和肿瘤球大小。从机制上讲，我们发现DAPT，一种γ-分泌酶（一种多亚基蛋白酶复合物）抑制剂，以时间和剂量依赖性的方式降低了人类GSC中细胞表面Nestin阳性细胞的比例，而总Nestin表达没有显著变化，这意味着翻译后修饰参与了细胞表面Nestin的生成。总之，我们的数据提供了第一个证据表明，细胞表面巢蛋白可能作为一个有前途的GSC标记物的异质性胶质母细胞瘤中的GSC的分离和表征。(C)2013 Elsevier Inc. All rights reserved.
Cancer stem cells (CSCs) are the most aggressive cell type in many malignancies. Cell surface proteins are generally used to isolate and characterize CSCs. Therefore, the identification of CSC-specific cell surface markers is very important for the diagnosis and treatment of malignancies. We found that Nestin (a type VI intermediate filament protein), like the glioma stem cell (GSC) markers CD133 and CD15, exhibited different levels of expression in primary human glioblastoma specimens. Similar to our previous finding that cytoplasmic Nestin is expressed as a cell surface form in mouse GSCs, the cell surface form of Nestin was also expressed at different levels in human GSCs. We isolated cell surface Nestin-positive cell populations from human GSCs by fluorescence-activated cell sorting FACS analysis, and observed that these populations exhibited robust CSC properties, such as increased tumorsphere-forming ability and tumorsphere size. Mechanistically, we found that DAPT, a gamma-secretase (a multi-subunit protease complex) inhibitor, reduced the proportion of cell surface Nestin-positive cells in human GSCs in a time- and dose-dependent manner, without significant changes in total Nestin expression, implying that a post-translational modification was involved in the generation of cell surface Nestin. Taken together, our data provides the first evidence that cell surface Nestin may serve as a promising GSC marker for the isolation and characterization of heterogeneous GSCs in glioblastomas. (C) 2013 Elsevier Inc. All rights reserved.