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Open Access Highly Accessed Research article

CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

Cristina Patru19, Luciana Romao12, Pascale Varlet13, Laure Coulombel1, Eric Raponi4, Josette Cadusseau5, François Renault-Mihara1, Cécile Thirant1, Nadine Leonard13, Alain Berhneim6, Maria Mihalescu-Maingot1, Jacques Haiech7, Ivan Bièche8, Vivaldo Moura-Neto2, Catherine Daumas-Duport13, Marie-Pierre Junier13 and Hervé Chneiweiss1*

Author Affiliations

1 Glial Plasticity lab; Inserm UMR 894; University Paris Descartes; Paris, France

2 Department of Anatomy, UFRJ, Rio, Brazil

3 Department of Neuropathology, Sainte-Anne Hospital, Paris, France

4 Grenoble - Institut de Neurosciences INSERM U83638706 La Tronche cedex, France

5 Inserm U955, Team 10, University of Paris 12, Créteil, France

6 Laboratoire de génomique cellulaire des cancers (FRE 2939 CNRS), Institut Gustave Roussy, Villejuif, France

7 CNRS UMR 7175; Institut Gilbert Laustriat; University Strasbourg I; Illkirch, France

8 Génétique et Biothérapies des Maladies Dégénératives et Prolifératives du Système Nerveux INSERM U745; IFR71; Université Paris Descartes; Paris, France

9 Present address: Department of Neurosurgery, Annecy, France

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BMC Cancer 2010, 10:66  doi:10.1186/1471-2407-10-66

Published: 24 February 2010

Abstract

Background

Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies.

Methods

We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas.

Results

A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide.

Conclusions

Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.