The Chemokine Receptor CXCR4 Strongly Promotes Neuroblastoma Primary Tumour and Metastatic Growth, but not Invasion.

The Chemokine Receptor CXCR4 Strongly Promotes Neuroblastoma Primary Tumour and Metastatic Growth, but not Invasion. Research Abstract Details 

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The Chemokine Receptor CXCR4 Strongly Promotes Neuroblastoma Primary Tumour and Metastatic Growth, but not Invasion. Abstract Text:

Roland Meier,Annick ,Marjorie Flahaut, Coulon,Carlo Fusco,Fawzia Louache,Katya Auderset,Katia Balmas Bourloud,Estelle Daudigeos,Curzio Ruegg,Gilles Vassal,Nicole Gross,Jean-Marc Joseph,Roland Meier,Annick ,Marjorie Flahaut, Coulon,Carlo Fusco,Fawzia Louache,Katya Auderset,Katia Balmas Bourloud,Estelle Daudigeos,Curzio Ruegg,Gilles Vassal,Nicole Gross,Jean-Marc Joseph,

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.

The Chemokine Receptor CXCR4 Strongly Promotes Neuroblastoma Primary Tumour and Metastatic Growth, but not Invasion. Publishing Authors By Initials

R Meier,A ,M Flahaut,A Coulon,C Fusco,F Louache,K Auderset,KB Bourloud,E Daudigeos,C Ruegg,G Vassal,N Gross,JM Joseph,R Meier,A ,M Flahaut,A Coulon,C Fusco,F Louache,K Auderset,KB Bourloud,E Daudigeos,C Ruegg,G Vassal,N Gross,JM Joseph,

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The Chemokine Receptor CXCR4 Strongly Promotes Neuroblastoma Primary Tumour and Metastatic Growth, but not Invasion. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: PLoS ONE

VOLUME: 2

Page Numbers: e1016

Journal Abbreviation: PLoS ONE

ISSN: 1932-6203

DAY: 10

MONTH: 10

YEAR: 2007

The Chemokine Receptor CXCR4 Strongly Promotes Neuroblastoma Primary Tumour and Metastatic Growth, but not Invasion. Information

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LANGUAGE: eng

NlmUniqueID: 101285081

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Grant and Affiliation Information for The Chemokine Receptor CXCR4 Strongly Promotes Neuroblastoma Primary Tumour and Metastatic Growth, but not Invasion.

AFFILIATION: Department of Paediatrics, Paediatric Oncology Research, University Hospital Centre Hospitalier Universitaire Vaudois Lausanne (CHUV), Lausanne, Switzerland.

Country: United States

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MEDLINETA: PLoS ONE

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