Cancer stem cells are enriched in the side population cells in a mouse model of glioma.
Cancer stem cells are enriched in the side population cells in a mouse model of glioma.
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DOI：
10.1158/0008-5472.can-08-0786
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发表时间：
2008-12-15
期刊：
影响因子：
11.2
通讯作者：
Yun K
中科院分区：
文献类型：
--
作者：
Harris MA;Yang H;Low BE;Mukherjee J;Guha A;Bronson RT;Shultz LD;Israel MA;Yun K
最近在多种人类癌症中鉴定出的癌症干细胞（CSCs）为在细胞水平上理解肿瘤发生提供了新的进展。CSC由其自我更新、多潜能性和移植后肿瘤起始的特征定义。通过测试这些定义特征，我们提供了在胶质瘤转基因小鼠模型S100 β-verbB; Trp 53中存在CSC的证据。在该胶质瘤模型中，CSC富集在侧群（SP）细胞中。与来自相同肿瘤的非SP细胞相比，这些SP细胞具有增强的肿瘤起始能力、自我更新和多潜能性。此外，比较FACS分选的癌SP细胞与非SP癌细胞和正常神经SP细胞的基因表达分析鉴定了45个在胶质瘤干细胞中差异表达的候选基因。我们验证了该列表中的两个基因（S100 a4和S100 a6）在原发性小鼠神经胶质瘤和人类神经胶质瘤样品中的表达。对异种移植的人GBM（多形性胶质母细胞瘤）细胞系和原代人胶质瘤组织的分析表明，S100 A4和S100 A6在一小部分癌细胞中表达，并且它们的丰度与肿瘤分级正相关。总之，本研究表明CSCs存在于小鼠胶质瘤模型中，表明该模型可用于研究体内CSCs的分子和细胞特征，并进一步验证癌症干细胞假说。
The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100ß-verbB;Trp53. In this glioma model, CSCs are enriched in the side-population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared to non-SP cells from the same tumors. Furthermore, gene expression analysis comparing FACS-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human GBM (glioblatoma multiforme) cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the cancer stem cell hypothesis.