title: Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors.
abstract: BACKGROUND
  Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined.
  
  
  RESULTS
  Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting.
  
  
  CONCLUSIONS
  In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.
authors.affiliation: Inserm, UMR894, Team Glial Plasticity, University Paris Descartes, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Thirant
authors.forename: Barbara
authors.initials: B
authors.lastname: Bessette
authors.forename: Pascale
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authors.lastname: Varlet
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Puget
authors.forename: Josette
authors.initials: J
authors.lastname: Cadusseau
authors.forename: Silvina Dos Reis
authors.initials: Sdos R
authors.lastname: Tavares
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Studler
authors.forename: David Carlos
authors.initials: DC
authors.lastname: Silvestre
authors.forename: Aurélie
authors.initials: A
authors.lastname: Susini
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Catherine
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authors.lastname: Miquel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bogeas
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Surena
authors.forename: Amélia
authors.initials: A
authors.lastname: Dias-Morais
authors.forename: Nadine
authors.initials: N
authors.lastname: Léonard
authors.forename: Françoise
authors.initials: F
authors.lastname: Pflumio
authors.forename: Ivan
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authors.lastname: Bièche
authors.forename: François D
authors.initials: FD
authors.lastname: Boussin
authors.forename: Christian
authors.initials: C
authors.lastname: Sainte-Rose
authors.forename: Jacques
authors.initials: J
authors.lastname: Grill
authors.forename: Catherine
authors.initials: C
authors.lastname: Daumas-Duport
authors.forename: Hervé
authors.initials: H
authors.lastname: Chneiweiss
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Junier
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000473:pathology*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005910:Glioma / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D014411:Neoplastic Stem Cells / Q000473:pathology*; D058953:Neural Stem Cells; D016019:Survival Analysis