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

<p>Abstract</p> <p>Background</p> <p>ASPM (<it>Abnormal Spindle-like Microcephaly associated</it>) over-expression was recently implicated in the development of malignant gliomas.</p> <p>Results</p> <p>To better characterize the invol...

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Main Authors: Calvo Charles, Boisselier Blandine, Idbaih Ahmed, Rousseau Audrey, Ravassard Philippe, Vampouille Raphaël, Marie Yannick, Colin Carole, Bikeye Sandra-Nadia, Leuraud Pascal, Lassalle Myriam, El Hallani Soufiane, Delattre Jean-Yves, Sanson Marc
Format: Article
Language:English
Published: BMC 2010-01-01
Series:Cancer Cell International
Online Access:http://www.cancerci.com/content/10/1/1
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Summary:<p>Abstract</p> <p>Background</p> <p>ASPM (<it>Abnormal Spindle-like Microcephaly associated</it>) over-expression was recently implicated in the development of malignant gliomas.</p> <p>Results</p> <p>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. <it>Aspm </it>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 <it>in vitro </it>and in mouse xenografts <it>in vivo</it>. Lentivirus-mediated shRNA silencing of ASPM resulted in dramatic proliferation arrest and cell death in two different gliomasphere models.</p> <p>Conclusion</p> <p>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.</p>
ISSN:1475-2867