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

doi:10.1186/1475-2867-10-1

Cancer Cell International

Volume 10

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

Sandra-Nadia Ngwabyt Bikeye¹ , Carole Colin² , Yannick Marie¹ , Raphaël Vampouille⁴ , Philippe Ravassard⁴ , Audrey Rousseau⁵ , Blandine Boisselier¹ , Ahmed Idbaih¹^,3 , Charles Félix Calvo¹ , Pascal Leuraud⁶ , Myriam Lassalle⁶ , Soufiane El Hallani¹ , Jean-Yves Delattre¹^,3 and Marc Sanson¹^,3

¹UMR975 INSERM-UPMC, GH Pitié- Salpêtrière, Paris

²UMR911-CRO2, Faculté de Médecine Timone, Université de la Méditerranée, Marseille

³Service de Neurologie Mazarin, GH Pitié- Salpêtrière, APHP, Paris

⁴Biotechnology & Biotherapy laboratory, Centre de Recherche de l'Institut du Cerveau et de la Moelle, CNRS UMR9225, INSERM UMRS 975 Université Pierre et Marie Curie, Hôpital de la Salpêtrière, Paris

⁵Service de Neuropathologie Raymond Escourolle, GH Pitié- Salpêtrière, Paris

⁶XenTech, Evry, France

author email corresponding author email

Cancer Cell International 2010, 10:1doi:10.1186/1475-2867-10-1


Published:	11 January 2010

Abstract

Background

ASPM (Abnormal Spindle-like Microcephaly associated) over-expression was recently implicated in the development of malignant gliomas.

Results

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.

Conclusion

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.