A restricted cell population propagates glioblastoma growth after chemotherapy.
A restricted cell population propagates glioblastoma growth after chemotherapy.
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DOI：
10.1038/nature11287
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发表时间：
2012-08-23
期刊：
影响因子：
64.8
通讯作者：
Parada, Luis F.
中科院分区：
文献类型：
--
作者：
Chen, Jian;Li, Yanjiao;Yu, Tzong-Shiue;McKay, Renee M.;Burns, Dennis K.;Kernie, Steven G.;Parada, Luis F.
多形性胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，中位生存期约为一年。这种不良的预后是由于治疗耐药和手术切除后肿瘤复发造成的。确切地说，复发是如何发生的尚不清楚。使用神经胶质瘤基因工程小鼠模型，我们鉴定了内源性肿瘤细胞的子集，在施用药物替莫唑胺（TMZ）暂时阻止肿瘤生长后，这些细胞是新肿瘤细胞的来源。标记静止室下区成体神经干细胞的 Nestin-ΔTK-IRES-GFP (Nes-ΔTK-GFP) 转基因也标记内源性神经胶质瘤肿瘤细胞的子集。在用 TMZ 抑制肿瘤细胞增殖后，脉冲追踪实验证明了源自 Nes-ΔTK-GFP 转基因亚群的肿瘤再生长细胞层次结构。长期给予更昔洛韦来消融 GFP+ 细胞可显着抑制肿瘤生长，而联合 TMZ-更昔洛韦治疗则可阻止肿瘤发展。这些数据表明存在相对静止的内源性神经胶质瘤细胞子集，它们通过产生短暂的高度增殖细胞群来维持肿瘤的长期生长。
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, with a median survival of about one year. This poor prognosis is due to therapeutic resistance and tumor recurrence following surgical removal. Precisely how recurrence occurs is unknown. Using a genetically-engineered mouse model of glioma, we identify a subset of endogenous tumor cells that are the source of new tumor cells after the drug, temozolomide (TMZ), is administered to transiently arrest tumor growth. A Nestin-ΔTK-IRES-GFP (Nes-ΔTK-GFP) transgene that labels quiescent subventricular zone adult neural stem cells also labels a subset of endogenous glioma tumor cells. Upon arrest of tumor cell proliferation with TMZ, pulse-chase experiments demonstrate a tumor re-growth cell hierarchy originating with the Nes-ΔTK-GFP transgene subpopulation. Ablation of the GFP+ cells with chronic ganciclovir administration significantly arrested tumor growth and combined TMZ-ganciclovir treatment impeded tumor development. These data indicate the existence of a relatively quiescent subset of endogenous glioma cells that are responsible for sustaining long-term tumor growth through the production of transient populations of highly proliferative cells.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
25
作者：
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通讯作者：
Sofroniew, MV
影响因子：
11.2
作者：
Kwon, Chang-Hyuk;Zhao, Dawen;Parada, Luis F.
通讯作者：
Parada, Luis F.