Functional sphere profiling reveals the complexity of neuroblastoma tumor-initiating cell model.

Details

Serval ID
serval:BIB_04199AE39171
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Functional sphere profiling reveals the complexity of neuroblastoma tumor-initiating cell model.
Journal
Neoplasia
Author(s)
Coulon A., Flahaut M., Mühlethaler-Mottet A., Meier R., Liberman J., Balmas-Bourloud K., Nardou K., Yan P., Tercier S., Joseph J.M., Sommer L., Gross N.
ISSN
1476-5586 (Electronic)
ISSN-L
1476-5586
Publication state
Published
Issued date
2011
Volume
13
Number
10
Pages
991-1004
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Neuroblastoma (NB) is a neural crest-derived childhood tumor characterized by a remarkable phenotypic diversity, ranging from spontaneous regression to fatal metastatic disease. Although the cancer stem cell (CSC) model provides a trail to characterize the cells responsible for tumor onset, the NB tumor-initiating cell (TIC) has not been identified. In this study, the relevance of the CSC model in NB was investigated by taking advantage of typical functional stem cell characteristics. A predictive association was established between self-renewal, as assessed by serial sphere formation, and clinical aggressiveness in primary tumors. Moreover, cell subsets gradually selected during serial sphere culture harbored increased in vivo tumorigenicity, only highlighted in an orthotopic microenvironment. A microarray time course analysis of serial spheres passages from metastatic cells allowed us to specifically "profile" the NB stem cell-like phenotype and to identify CD133, ABC transporter, and WNT and NOTCH genes as spheres markers. On the basis of combined sphere markers expression, at least two distinct tumorigenic cell subpopulations were identified, also shown to preexist in primary NB. However, sphere markers-mediated cell sorting of parental tumor failed to recapitulate the TIC phenotype in the orthotopic model, highlighting the complexity of the CSC model. Our data support the NB stem-like cells as a dynamic and heterogeneous cell population strongly dependent on microenvironmental signals and add novel candidate genes as potential therapeutic targets in the control of high-risk NB.
Pubmed
Web of science
Create date
05/01/2012 17:48
Last modification date
20/08/2019 13:25
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