Involvement of the CXCR7/CXCR4/CXCL12 Axis in the Malignant Progression of Human Neuroblastoma.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_841497C75C78
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Involvement of the CXCR7/CXCR4/CXCL12 Axis in the Malignant Progression of Human Neuroblastoma.
Périodique
Plos One
Auteur(s)
Liberman J., Sartelet H., Flahaut M., Mühlethaler-Mottet A., Coulon A., Nyalendo C., Vassal G., Joseph J.M., Gross N.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2012
Volume
7
Numéro
8
Pages
e43665
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish. Author Contributions: Conceived and designed the experiments: JL JMJ NG. Performed the experiments: JL JMJ. Analyzed the data: JL HS MF AMM AC CN JMJ NG. Contributed reagents/materials/analysis tools: HS GV NG. Wrote the paper: JL NG. Revised the manuscript: HS MF AMM AC GV JMJ NG. Gave final approval of the manuscript: JMJ NG.
Résumé
Neuroblastoma (NB) is a typical childhood and heterogeneous neoplasm for which efficient targeted therapies for high-risk tumors are not yet identified. The chemokine CXCL12, and its receptors CXCR4 and CXCR7 have been involved in tumor progression and dissemination. While CXCR4 expression is associated to undifferentiated tumors and poor prognosis, the role of CXCR7, the recently identified second CXCL12 receptor, has not yet been elucidated in NB. In this report, CXCR7 and CXCL12 expressions were evaluated using a tissue micro-array including 156 primary and 56 metastatic NB tissues. CXCL12 was found to be highly associated to NB vascular and stromal structures. In contrast to CXCR4, CXCR7 expression was low in undifferentiated tumors, while its expression was stronger in matured tissues and specifically associated to differentiated neural tumor cells. As determined by RT-PCR, CXCR7 expression was mainly detected in N-and S-type NB cell lines, and was slightly induced upon NB cell differentiation in vitro. The relative roles of the two CXCL12 receptors were further assessed by overexpressing CXCR7 or CXCR4 receptor alone, or in combination, in the IGR-NB8 and the SH-SY5Y NB cell lines. In vitro functional analyses indicated that, in response to their common ligand, both receptors induced activation of ERK1/2 cascade, but not Akt pathway. CXCR7 strongly reduced in vitro growth, in contrast to CXCR4, and impaired CXCR4/CXCL12-mediated chemotaxis. Subcutaneous implantation of CXCR7-expressing NB cells showed that CXCR7 also significantly reduced in vivo growth. Moreover, CXCR7 affected CXCR4-mediated orthotopic growth in a CXCL12-producing environment. In such model, CXCR7, in association with CXCR4, did not induce NB cell metastatic dissemination. In conclusion, the CXCR7 and CXCR4 receptors revealed specific expression patterns and distinct functional roles in NB. Our data suggest that CXCR7 elicits anti-tumorigenic functions, and may act as a regulator of CXCR4/CXCL12-mediated signaling in NB.
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/09/2012 19:09
Dernière modification de la notice
08/05/2019 21:18
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