ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target.

ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target.
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DOI:
10.1186/1475-2867-10-1
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发表时间:
2010-01-11
影响因子:
5.8
通讯作者:
Sanson M
Sanson M
中科院分区:
医学2区
文献类型:
--
作者:
Bikeye SN;Colin C;Marie Y;Vampouille R;Ravassard P;Rousseau A;Boisselier B;Idbaih A;Calvo CF;Leuraud P;Lassalle M;El Hallani S;Delattre JY;Sanson M

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ASPM(异常梭形小头畸形相关)过度表达最近被牵连在恶性胶质瘤的发展。为了更好地表征ASPM在胶质瘤中的参与,我们研究了175个样本中的mRNA表达,包括8个WHO II级,75个WHO III级和92个WHO IV级肿瘤。aspm表达与肿瘤分级密切相关,无论原发肿瘤的初始分级如何,与初始病变相比,aspm表达在复发时增加。ASPM的表达也增加了一系列传代胶质球在体外和小鼠异种移植物在体内。慢病毒介导的ASPM的shRNA沉默在两种不同的胶质瘤球模型中导致显著的增殖停滞和细胞死亡。这些数据表明,ASPM参与胶质瘤的恶性进展,可能通过癌症干细胞区室的扩增,并且是多形性胶质母细胞瘤中有吸引力的治疗靶点。
ASPM (Abnormal Spindle-like Microcephaly associated) over-expression was recently implicated in the development of malignant gliomas. To better characterize the involvement of ASPM in gliomas, we investigated the mRNA expression in 175 samples, including 8 WHO Grade II, 75 WHO Grade III and 92 WHO Grade IV tumors. Aspm expression was strongly correlated with tumor grade and increased at recurrence when compared to the initial lesion, whatever the initial grade of the primary tumor. ASPM expression also increased over serial passages in gliomaspheres in vitro and in mouse xenografts in vivo. Lentivirus-mediated shRNA silencing of ASPM resulted in dramatic proliferation arrest and cell death in two different gliomasphere models. These data suggest that ASPM is involved in the malignant progression of gliomas, possibly through expansion of a cancer stem cell compartment, and is an attractive therapeutic target in glioblastoma multiforme.
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