Isolation of cancer stem cells from adult glioblastoma multiforme

Isolation of cancer stem cells from adult glioblastoma multiforme
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DOI:
10.1038/sj.onc.1208311
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发表时间:
2004-12-16
期刊:
影响因子:
8
通讯作者:
Yu, JS
Yu, JS
中科院分区:
医学1区
文献类型:
--
作者:
Yuan, XP;Curtin, J;Yu, JS

文献摘要

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多形性胶质母细胞瘤(GBM)是最常见的成人原发性脑肿瘤,由异质细胞群组成。目前尚不清楚肿瘤团块中的哪些细胞负责肿瘤的发生和维持。在这项研究中,我们报道了可以从成人GBMs中鉴定出脑肿瘤干细胞。这些肿瘤干细胞形成神经球,具有自我更新的能力,表达与神经干细胞(NSCs)相关的基因,从一个母细胞产生不同表型的子细胞,并分化成与初始GBM中存在的细胞相似的表型多样化的细胞群。这些肿瘤干细胞具有与正常NSCs不同的特征,即使在诱导分化后也可以重组球体。此外,只有这些肿瘤干细胞在裸鼠体内植入后能够形成肿瘤并同时产生神经元和胶质细胞。成人GBM中肿瘤干细胞的鉴定可能是了解GBM起源和维持的重要一步,并导致新的治疗靶点的鉴定和测试。
Glioblastoma multiforme (GBM) is the most common adult primary brain tumor and is comprised of a heterogeneous population of cells. It is unclear which cells within the tumor mass are responsible for tumor initiation and maintenance. In this study, we report that brain tumor stem cells can be identified from adult GBMs. These tumor stem cells form neurospheres, possess the capacity for self-renewal, express genes associated with neural stem cells (NSCs), generate daughter cells of different phenotypes from one mother cell, and differentiate into the phenotypically diverse populations of cells similar to those present in the initial GBM. Having a distinguishing feature from normal NSCs, these tumor stem cells can reform spheres even after the induction of differentiation. Furthermore, only these tumor stem cells were able to form tumors and generate both neurons and glial cells after in vivo implantation into nude mice. The identification of tumor stem cells within adult GBM may represent a major step forward in understanding the origin and maintenance of GBM and lead to the identification and testing of new therapeutic targets.