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Cancer Cell International
Published in: Cancer Cell International 1/2010

Open Access 01-12-2010 | Primary research

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

Authors: Sandra-Nadia Ngwabyt Bikeye, Carole Colin, Yannick Marie, Raphaël Vampouille, Philippe Ravassard, Audrey Rousseau, Blandine Boisselier, Ahmed Idbaih, Charles Félix Calvo, Pascal Leuraud, Myriam Lassalle, Soufiane El Hallani, Jean-Yves Delattre, Marc Sanson

Published in: Cancer Cell International | Issue 1/2010

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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.
Appendix
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Literature
1.
Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A: Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 2004, 64 (19): 7011-7021. 10.1158/0008-5472.CAN-04-1364.CrossRefPubMed
2.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB: Identification of human brain tumour initiating cells. Nature. 2004, 432 (7015): 396-401. 10.1038/nature03128.CrossRefPubMed
3.
Fish JL, Kosodo Y, Enard W, Paabo S, Huttner WB: Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc Natl Acad Sci USA. 2006, 103 (27): 10438-10443. 10.1073/pnas.0604066103.PubMedCentralCrossRefPubMed
4.
Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K, Mahadevan M, Crow YJ, Markham AF: ASPM is a major determinant of cerebral cortical size. Nat Genet. 2002, 32 (2): 316-320. 10.1038/ng995.CrossRefPubMed
5.
Kouprina N, Pavlicek A, Collins NK, Nakano M, Noskov VN, Ohzeki J, Mochida GH, Risinger JI, Goldsmith P, Gunsior M: The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum Mol Genet. 2005, 14 (15): 2155-2165. 10.1093/hmg/ddi220.CrossRefPubMed
6.
Horvath S, Zhang B, Carlson M, Lu KV, Zhu S, Felciano RM, Laurance MF, Zhao W, Qi S, Chen Z: Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target. Proc Natl Acad Sci USA. 2006, 103 (46): 17402-17407. 10.1073/pnas.0608396103.PubMedCentralCrossRefPubMed
7.
Hagemann C, Anacker J, Gerngras S, Kuhnel S, Said HM, Patel R, Kammerer U, Vordermark D, Roosen K, Vince GH: Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas. Oncol Rep. 2008, 20 (2): 301-308.PubMed
8.
Idbaih A, Marie Y, Lucchesi C, Pierron G, Manie E, Raynal V, Mosseri V, Hoang-Xuan K, Kujas M, Brito I: BAC array CGH distinguishes mutually exclusive alterations that define clinicogenetic subtypes of gliomas. Int J Cancer. 2008, 122 (8): 1778-1786. 10.1002/ijc.23270.CrossRefPubMed
9.
Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D: Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol. 1997, 15 (9): 871-875. 10.1038/nbt0997-871.CrossRefPubMed
10.
Yee JK, Miyanohara A, LaPorte P, Bouic K, Burns JC, Friedmann T: A general method for the generation of high-titer, pantropic retroviral vectors: highly efficient infection of primary hepatocytes. Proc Natl Acad Sci USA. 1994, 91 (20): 9564-9568. 10.1073/pnas.91.20.9564.PubMedCentralCrossRefPubMed
11.
Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Charneau P: HIV-1 genome nuclear import is mediated by a central DNA flap. Cell. 2000, 101 (2): 173-185. 10.1016/S0092-8674(00)80828-4.CrossRefPubMed
12.
Castaing M, Guerci A, Mallet J, Czernichow P, Ravassard P, Scharfmann R: Efficient restricted gene expression in beta cells by lentivirus-mediated gene transfer into pancreatic stem/progenitor cells. Diabetologia. 2005, 48 (4): 709-719. 10.1007/s00125-005-1694-6.CrossRefPubMed
Metadata
Title
ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target
Authors
Sandra-Nadia Ngwabyt Bikeye
Carole Colin
Yannick Marie
Raphaël Vampouille
Philippe Ravassard
Audrey Rousseau
Blandine Boisselier
Ahmed Idbaih
Charles Félix Calvo
Pascal Leuraud
Myriam Lassalle
Soufiane El Hallani
Jean-Yves Delattre
Marc Sanson
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2010
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-10-1

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