Activation of neural and pluripotent stem cell signatures correlates with increased malignancy in human glioma.
Activation of neural and pluripotent stem cell signatures correlates with increased malignancy in human glioma.
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DOI：
10.1371/journal.pone.0018454
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发表时间：
2011-03-31
期刊：
影响因子：
3.7
通讯作者：
Muhr J
中科院分区：
文献类型：
--
作者：
Holmberg J;He X;Peredo I;Orrego A;Hesselager G;Ericsson C;Hovatta O;Oba-Shinjo SM;Marie SK;Nistér M;Muhr J
胶质瘤细胞中干细胞特征的存在提高了促进组织特异性干细胞维持和自我更新的机制在肿瘤细胞中具有类似功能的可能性。在这里，我们描述了不同恶性级别的人类胶质瘤干细胞调节蛋白的表达。我们发现，高级别胶质瘤细胞共表达一系列神经干细胞（NSCs）标志物，这些蛋白在肿瘤细胞中可以实现与NSCs相似的功能。然而，与NSCs相反，胶质瘤细胞与多能干细胞标记物共同表达神经蛋白，包括转录因子Oct4、Sox2、Nanog和Klf4。与这一发现一致，在高级别胶质瘤中，中胚层和内胚层特异性转录因子与神经蛋白一起被检测到，这是一种通常不存在于中枢神经系统的谱系标记的组合。多能干细胞特性的持续存在只能在实体肿瘤中检测到，基于体外研究和小鼠异种移植物移植的观察表明，这种存在依赖于内在和外在调节信号的联合活性。总之，这些结果证明了神经和多能干细胞特征在恶性人类胶质瘤中的普遍失调表达，并表明干细胞调节因子可能为治疗策略提供重要的靶点。
The presence of stem cell characteristics in glioma cells raises the possibility that mechanisms promoting the maintenance and self-renewal of tissue specific stem cells have a similar function in tumor cells. Here we characterized human gliomas of various malignancy grades for the expression of stem cell regulatory proteins. We show that cells in high grade glioma co-express an array of markers defining neural stem cells (NSCs) and that these proteins can fulfill similar functions in tumor cells as in NSCs. However, in contrast to NSCs glioma cells co-express neural proteins together with pluripotent stem cell markers, including the transcription factors Oct4, Sox2, Nanog and Klf4. In line with this finding, in high grade gliomas mesodermal- and endodermal-specific transcription factors were detected together with neural proteins, a combination of lineage markers not normally present in the central nervous system. Persistent presence of pluripotent stem cell traits could only be detected in solid tumors, and observations based on in vitro studies and xenograft transplantations in mice imply that this presence is dependent on the combined activity of intrinsic and extrinsic regulatory cues. Together these results demonstrate a general deregulated expression of neural and pluripotent stem cell traits in malignant human gliomas, and indicate that stem cell regulatory factors may provide significant targets for therapeutic strategies.
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DOI：
10.4161/cc.8.20.9701
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Heddleston JM;Li Z;McLendon RE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
影响因子：
4
作者：
Liu, Tong Ming;Wu, Ying Nan;Lim, Bing
通讯作者：
Lim, Bing
Sox2 在人胶质瘤起始细胞中被真核起始因子 4E 翻译激活
DOI：
10.1016/j.bbrc.2010.06.015
发表时间：
2010-07-09
影响因子：
3.1
作者：
Ge, Yuqing;Zhou, Fengbiao;Jiang, Jianhai
通讯作者：
Jiang, Jianhai
影响因子：
5.4
作者：
Kim, R;Trubetskoy, A;Lenz, J
通讯作者：
Lenz, J
影响因子：
5.2
作者：
Inzunza, J;Gertow, K;Hovatta, O
通讯作者：
Hovatta, O