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ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target |
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| Authors: | Sandra-Nadia Ngwabyt Bikeye Carole Colin Yannick Marie Raphaël Vampouille Philippe Ravassard Audrey Rousseau Blandine Boisselier Ahmed Idbaih Félix Charles Calvo Pascal Leuraud Myriam Lassalle Soufiane El Hallani Jean-Yves Delattre Marc Sanson |
| Institution: | 1. GH Pitié- Salpêtrière, UMR975 INSERM-UPMC, Paris 2. UMR911-CRO2, Faculté de Médecine Timone, Université de la Méditerranée, Marseille 4. Biotechnology & Biotherapy laboratory, Centre de Recherche de l'Institut du Cerveau et de la Moelle, CNRS UMR9225, INSERM UMRS 975 Université Pierre et Marie Curie, H?pital de la Salpêtrière, Paris 5. Service de Neuropathologie Raymond Escourolle, GH Pitié- Salpêtrière, Paris 3. Service de Neurologie Mazarin, GH Pitié- Salpêtrière, APHP, Paris 6. XenTech, Evry, France |
| 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. |
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