Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors

Cécile Thirant, Barbara Bessette, Pascale Varlet, Stéphanie Puget, Josette Cadusseau, Silvina dos Reis Tavares, Jeanne Marie Studler, David Carlos Silvestre, Aurélie Susini, Chiara Villa, Catherine Miquel, Alexandra Bogeas, Anne Laure Surena, Amélia Dias-Morais, Nadine Léonard, Françoise Pflumio, Ivan Biéche, François D. Boussin, Christian Sainte-Rose, Jacques GrillCatherine Daumas-Duport, Hervé Chneiweiss, Marie Pierre Junier

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    55 Citations (Scopus)

    Résumé

    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. Methodology/Principal Findings: 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 selfrenewals), 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, chisquare 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/Significance: 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.

    langue originaleAnglais
    Numéro d'articlee16375
    journalPLoS ONE
    Volume6
    Numéro de publication1
    Les DOIs
    étatPublié - 7 févr. 2011

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