Quiescent human glioblastoma cancer stem cells drive tumor initiation, expansion, and recurrence following chemotherapy.
Quiescent human glioblastoma cancer stem cells drive tumor initiation, expansion, and recurrence following chemotherapy.
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DOI：
10.1016/j.devcel.2021.12.007
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发表时间：
2022-01-10
影响因子：
11.8
通讯作者：
Parada LF
中科院分区：
文献类型：
--
作者：
Xie XP;Laks DR;Sun D;Ganbold M;Wang Z;Pedraza AM;Bale T;Tabar V;Brennan C;Zhou X;Parada LF
我们验证了胶质母细胞瘤含有逃避抗增殖治疗的静止癌症干细胞的假设。基因工程小鼠自发胶质母细胞瘤的功能表征揭示了可直接从肿瘤中分离出的基本静止干细胞样细胞。在预先形成的缺乏增殖基因表达的患者异种移植单细胞簇中，衍生的静止癌症干细胞特异性基因表达特征丰富。在原发和复发的人类胶质母细胞瘤的静止单细胞群中保存了一个精炼的人类118基因特征。F3细胞表面受体mRNA在保守特征中表达，通过抗体免疫组化识别静止肿瘤细胞。F3抗体分类的胶质母细胞瘤细胞表现出干细胞基因表达，在培养中增强自我更新，驱动肿瘤起始，连续移植，重构肿瘤异质性。化疗后，存留的癌症干细胞池被激活并加速向增殖的过渡。这些结果有助于解释常规治疗的失败，并为替代疗法奠定了概念框架。肿瘤复发是胶质母细胞瘤（GBM）治疗的难题。Xie， Laks等人描述了小鼠和人类GBM中静止的癌症干细胞，这些干细胞在化疗后被激活，从而为癌症干细胞在GBM复发中的作用和识别潜在的可操作脆弱性铺平了道路。
We test the hypothesis that glioblastoma harbors quiescent cancer stem cells that evade anti-proliferative therapies. Functional characterization of spontaneous glioblastomas from genetically engineered mice reveals essential quiescent stem-like cells that can be directly isolated from tumors. A derived quiescent cancer stem cell specific gene expression signature is enriched in pre-formed patient xenograft single cell clusters that lack proliferative gene expression. A refined human 118-gene signature is preserved in quiescent single cell populations from primary and recurrent human glioblastomas. The F3 cell surface receptor mRNA, expressed in the conserved signature, identifies quiescent tumor cells by antibody immunohistochemistry. F3 antibody sorted glioblastoma cells exhibit stem cell gene expression, enhanced self-renewal in culture, drive tumor initiation, serial transplantation, and reconstitute tumor heterogeneity. Upon chemotherapy, the spared cancer stem cell pool becomes activated and accelerates transition to proliferation. These results help explain conventional treatment failure and lay a conceptual framework for alternative therapies. Tumor recurrence is a challenge in glioblastoma (GBM) treatment. Xie, Laks et al. characterize quiescent cancer stem cells, in both mouse and human GBM, that become activated upon chemotherapy, thus paving the way for interrogation of the cancer stem cell role in GBM recurrence and the identification of potentially actionable vulnerabilities.
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影响因子：
64.8
作者：
Lan X;Jörg DJ;Cavalli FMG;Richards LM;Nguyen LV;Vanner RJ;Guilhamon P;Lee L;Kushida MM;Pellacani D;Park NI;Coutinho FJ;Whetstone H;Selvadurai HJ;Che C;Luu B;Carles A;Moksa M;Rastegar N;Head R;Dolma S;Prinos P;Cusimano MD;Das S;Bernstein M;Arrowsmith CH;Mungall AJ;Moore RA;Ma Y;Gallo M;Lupien M;Pugh TJ;Taylor MD;Hirst M;Eaves CJ;Simons BD;Dirks PB
通讯作者：
Dirks PB
DOI：
10.1038/nrm3591
发表时间：
2013-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.8
作者：
Ferron, Sacri R.;Andreu-Agullo, Celia;Farinas, Isabel
通讯作者：
Farinas, Isabel
影响因子：
64.5
作者：
Azizi E;Carr AJ;Plitas G;Cornish AE;Konopacki C;Prabhakaran S;Nainys J;Wu K;Kiseliovas V;Setty M;Choi K;Fromme RM;Dao P;McKenney PT;Wasti RC;Kadaveru K;Mazutis L;Rudensky AY;Pe'er D
通讯作者：
Pe'er D
影响因子：
8.8
作者：
MacLeod, Graham;Bozek, Danielle A.;Angers, Stephane
通讯作者：
Angers, Stephane