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

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Ressource 1Download: Plos One 2007.pdf (419.64 [Ko])
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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_D52F7A4D0720
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The chemokine receptor CXCR4 strongly promotes neuroblastoma primary tumour and metastatic growth, but not invasion.
Journal
PloS one
Author(s)
Meier R, Mühlethaler-Mottet A, Flahaut M, Coulon A, Fusco C, Louache F, Auderset K, Bourloud KB, Daudigeos E, Ruegg C, Vassal G, Gross N, Joseph JM
Publication state
Published
Issued date
10/2007
Peer-reviewed
Oui
Language
english
Abstract
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.
Keywords
CXCR4, CXCL12, neuroblastoma
Pubmed
Open Access
Yes
Create date
23/03/2020 12:44
Last modification date
26/06/2020 7:10
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