Back to Search Start Over

Functional Sphere Profiling Reveals the Complexity of Neuroblastoma Tumor-Initiating Cell Model

Authors :
Aurélie Coulon
Marjorie Flahaut
Annick Mühlethaler-Mottet
Roland Meier
Julie Liberman
Katia Balmas-Bourloud
Katya Nardou
Pu Yan
Stéphane Tercier
Jean-Marc Joseph
Lukas Sommer
Nicole Gross
Source :
Neoplasia: An International Journal for Oncology Research, Vol 13, Iss 10, Pp 991-1004 (2011)
Publication Year :
2011
Publisher :
Elsevier, 2011.

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.

Details

Language :
English
ISSN :
14765586 and 15228002
Volume :
13
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Neoplasia: An International Journal for Oncology Research
Publication Type :
Academic Journal
Accession number :
edsdoj.b86551d97c943c19f5bb4a2481aa1af
Document Type :
article
Full Text :
https://doi.org/10.1593/neo.11800