The chemokine receptor CXCR4 strongly promotes neuroblastoma primary tumour and metastatic growth, but not invasion.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_75476A10628B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The chemokine receptor CXCR4 strongly promotes neuroblastoma primary tumour and metastatic growth, but not invasion.
Périodique
PLoS ONE
Auteur(s)
Meier R., Mühlethaler-Mottet A., Flahaut M., Coulon A., Fusco C., Louache F., Auderset K., Bourloud K.B., Daudigeos E., Ruegg C., Vassal G., Gross N., Joseph J.M.
ISSN
1932-6203[electronic]
Statut éditorial
Publié
Date de publication
2007
Volume
2
Numéro
10
Pages
e1016
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: epublish
Résumé
Neuroblastoma (NB) is a heterogeneous, and particularly malignant childhood neoplasm in its higher stages, with a propensity to form metastasis in selected organs, in particular liver and bone marrow, and for which there is still no efficient treatment available beyond surgery. Recent evidence indicates that the CXCR4/CXCL12 chemokine/receptor axis may be involved in promoting NB invasion and metastasis. In this study, we explored the potential role of CXCR4 in the malignant behaviour of NB, using a combination of in vitro functional analyses and in vivo growth and metastasis assessment in an orthotopic NB mouse model. We show here that CXCR4 overexpression in non-metastatic CXCR4-negative NB cells IGR-NB8 and in moderately metastatic, CXCR4 expressing NB cells IGR-N91, strongly increased tumour growth of primary tumours and liver metastases, without altering the frequency or the pattern of metastasis. Moreover shRNA-mediated knock-down experiments confirmed our observations by showing that silencing CXCR4 in NB cells impairs in vitro and almost abrogates in vivo growth. High levels of CXCL12 were detected in the mouse adrenal gland (the primary tumour site), and in the liver suggesting a paracrine effect of host-derived CXCL12 on NB growth. In conclusion, this study reveals a yet unreported NB-specific predominant growth and survival-promoting role of CXCR4, which warrants a critical reconsideration of the role of CXCR4 in the malignant behaviour of NB and other cancers.
Mots-clé
Animals, Bone Marrow Cells, Cell Line, Tumor, Cell Proliferation, Disease Progression, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, Liver, Mice, Mice, Nude, Models, Biological, Neoplasm Invasiveness, Neoplasm Transplantation, Neuroblastoma, Receptors, CXCR4
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 9:36
Dernière modification de la notice
08/05/2019 20:30
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