Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-55119

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 (2011). Functional sphere profiling reveals the complexity of neuroblastoma tumor-initiating cell model. Neoplasia, 13(10):991-1004.

Published Version
View at publisher


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.


31 citations in Web of Science®
33 citations in Scopus®
Google Scholar™



113 downloads since deposited on 12 Jan 2012
24 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:October 2011
Deposited On:12 Jan 2012 09:19
Last Modified:05 Apr 2016 15:22
Publisher:Neoplasia Press
Publisher DOI:10.1593/neo.11800
PubMed ID:22028624

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page