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.
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.
Patru
Cristina
C
Glial Plasticity lab, Inserm UMR 894, University Paris Descartes, Paris, France.
Romao
Luciana
L
Varlet
Pascale
P
Coulombel
Laure
L
Raponi
Eric
E
Cadusseau
Josette
J
Renault-Mihara
François
F
Thirant
Cécile
C
Leonard
Nadine
N
Berhneim
Alain
A
Mihalescu-Maingot
Maria
M
Haiech
Jacques
J
Bièche
Ivan
I
Moura-Neto
Vivaldo
V
Daumas-Duport
Catherine
C
Junier
Marie-Pierre
MP
Chneiweiss
Hervé
H
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D018952:Antigens, CD34 / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D016256:Lewis X Antigen / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology*; D009474:Neurons / Q000473:pathology*; D010455:Peptides; D040901:Proteomics / Q000379:methods
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D016256:Lewis X Antigen; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse