Abstract
BackgroundASPM (Abnormal Spindle-like Microcephaly associated) over-expression was recently implicated in the development of malignant gliomas.ResultsTo 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.ConclusionThese 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.
Highlights
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
ASPM expression increases with glioma grade We measured ASPM expression via qRT-PCR in 175 gliomas (8 Grade II, 75 Grade III and 92 Grade IV) and in three non-neoplastic brain tissues (NT)
ASPM is upregulated in recurrent gliomas relative to the initial tumor ASPM mRNA expression was measured in 11 recurrent tumors and compared to the initial tumor
Summary
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 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 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. ASPM (Abnormal Spindle-like Microcephaly associated) over-expression was recently implicated in the development of malignant gliomas
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