Glioma Stem Cell Lines Expanded in Adherent Culture Have Tumor-Specific Phenotypes and Are Suitable for Chemical and Genetic Screens
Glioma Stem Cell Lines Expanded in Adherent Culture Have Tumor-Specific Phenotypes and Are Suitable for Chemical and Genetic Screens
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DOI：
10.1016/j.stem.2009.03.014
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发表时间：
2009-06-05
期刊：
影响因子：
23.9
通讯作者：
Dirks, Peter
中科院分区：
文献类型：
--
作者：
Pollard, Steven M.;Yoshikawa, Koichi;Dirks, Peter
人类脑肿瘤似乎有一个分层的细胞组织，暗示了一个干细胞基础。在体外扩增假定的癌症干细胞作为稳定的细胞系将提供一个强大的模型系统，以研究其生物学。在这里，我们证明了常规和有效的衍生粘附细胞系恶性胶质瘤显示干细胞特性，并启动高级别胶质瘤异种移植后。值得注意的是，来自不同肿瘤的神经胶质瘤神经干（GNS）细胞系表现出与特定神经祖细胞亚型相关的不同基因表达特征和分化行为。因此，神经胶质瘤的多样性可能反映了不同的癌症干细胞表型。与“球形”培养物相比，贴壁GNS细胞系的纯度和稳定性提供了显著的优势，从而能够对癌症干细胞行为进行精细研究。一项基于活细胞成像的原理验证化学筛选（450种FDA批准的药物）鉴定了GNS细胞的不同敏感性和对5-羟色胺信号传导扰动的共同敏感性。
Human brain tumors appear to have a hierarchical cellular organization suggestive of a stern cell foundation. In vitro expansion of the putative cancer stem cells as stable cell lines would provide a powerful model system to study their biology. Here, we demonstrate routine and efficient derivation of adherent cell lines from malignant glioma that display stem cell properties and initiate high-grade gliomas following xenotransplantation. Significantly, glioma neural stem (GNS) cell lines from different tumors exhibit divergent gene expression signatures and differentiation behavior that correlate with specific neural progenitor subtypes. The diversity of gliomas may, therefore, reflect distinct cancer stem cell phenotypes. The purity and stability of adherent GNS cell lines offer significant advantages compared to "sphere" cultures, enabling refined studies of cancer stem cell behavior. A proof-of-principle live cell imaging-based chemical screen (450 FDA-approved drugs) identifies both differential sensitivities of GNS cells and a common susceptibility to perturbation of serotonin signaling.