%0 Journal Article
%T ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target
%A Sandra-Nadia Bikeye
%A Carole Colin
%A Yannick Marie
%A Rapha£żl Vampouille
%A Philippe Ravassard
%A Audrey Rousseau
%A Blandine Boisselier
%A Ahmed Idbaih
%A Charles Calvo
%A Pascal Leuraud
%A Myriam Lassalle
%A Soufiane El Hallani
%A Jean-Yves Delattre
%A Marc Sanson
%J Cancer Cell International
%D 2010
%I BioMed Central
%R 10.1186/1475-2867-10-1
%X 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.Gliomas are the most common type of primary tumors in the central nervous system (CNS), and their usual fate is to recur, either as a similar or more frequently as a higher grade lesion, explaining their grim prognosis. The cellular origin of gliomas remains unknown, but accumulating data suggest that transformed, stem-like precursors (CSC) may represent the cells that drive their growth [1,2].The product of ASPM gene (Abnormal Spindle-like Microcephaly associated) localizes to centrosomes, spindle poles, and the midbody [3]. By promoting neuroblast proliferation and driving the orientation of mitotic cleavage, it allows for symmetric, proliferative division of neuroepithelial cells during brain development, and consequently brain surface expansion [3]. Mutations within this gene produce primary microcephaly [4]. In addition to its role in embryonic development, ASPM is highly expressed in many tumor cell lines [5], suggesting an important involvement of this gene during tumorigenesis. Recent evidence suggests that ASPM is also overexpressed in malignant gliomas and that its knockdown inhibits tumor proliferation [6,7].In this study, we report that ASPM expression is c
%U http://www.cancerci.com/content/10/1/1