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Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas

Wnt signalling is an important component of vertebrate development, required for specification of the neural crest. Ten Wnt receptors [Frizzled receptor 1-10 (Fzd1-10)] have been identified so far, some of which are expressed in the developing nervous system and the neural crest. Here we show that e...

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Autores principales: Cantilena, Sandra, Pastorino, Fabio, Pezzolo, Annalisa, Chayka, Olesya, Pistoia, Vito, Ponzoni, Mirco, Sala, Arturo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282103/
https://www.ncbi.nlm.nih.gov/pubmed/22249030
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author Cantilena, Sandra
Pastorino, Fabio
Pezzolo, Annalisa
Chayka, Olesya
Pistoia, Vito
Ponzoni, Mirco
Sala, Arturo
author_facet Cantilena, Sandra
Pastorino, Fabio
Pezzolo, Annalisa
Chayka, Olesya
Pistoia, Vito
Ponzoni, Mirco
Sala, Arturo
author_sort Cantilena, Sandra
collection PubMed
description Wnt signalling is an important component of vertebrate development, required for specification of the neural crest. Ten Wnt receptors [Frizzled receptor 1-10 (Fzd1-10)] have been identified so far, some of which are expressed in the developing nervous system and the neural crest. Here we show that expression of one such receptors, Fzd6, predicts poor survival in neuroblastoma patients and marks rare, HIF1/2 α-positive cells in tumour hypoxic areas. Fzd6 positive neuroblastoma cells form neurospheres with high efficiency, are resistant to doxorubicin killing and express high levels of mesenchymal markers such as Twist1 and Notch1. Expression of Fzd6 is required for the expression of genes of the non-canonical Wnt pathway and the spheres forming activity. When transplanted into immunodeficient mice, neuroblastoma cells expressing the Fzd6 marker grow more aggressively than their Fzd6 negative counterparts. We conclude that Fzd6 is a new surface marker of aggressive neuroblastoma cells with stem cell-like features.
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spelling pubmed-32821032012-02-22 Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas Cantilena, Sandra Pastorino, Fabio Pezzolo, Annalisa Chayka, Olesya Pistoia, Vito Ponzoni, Mirco Sala, Arturo Oncotarget Brief Reports Wnt signalling is an important component of vertebrate development, required for specification of the neural crest. Ten Wnt receptors [Frizzled receptor 1-10 (Fzd1-10)] have been identified so far, some of which are expressed in the developing nervous system and the neural crest. Here we show that expression of one such receptors, Fzd6, predicts poor survival in neuroblastoma patients and marks rare, HIF1/2 α-positive cells in tumour hypoxic areas. Fzd6 positive neuroblastoma cells form neurospheres with high efficiency, are resistant to doxorubicin killing and express high levels of mesenchymal markers such as Twist1 and Notch1. Expression of Fzd6 is required for the expression of genes of the non-canonical Wnt pathway and the spheres forming activity. When transplanted into immunodeficient mice, neuroblastoma cells expressing the Fzd6 marker grow more aggressively than their Fzd6 negative counterparts. We conclude that Fzd6 is a new surface marker of aggressive neuroblastoma cells with stem cell-like features. Impact Journals LLC 2011-12-31 /pmc/articles/PMC3282103/ /pubmed/22249030 Text en Copyright: © 2011 Cantilena et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Brief Reports
Cantilena, Sandra
Pastorino, Fabio
Pezzolo, Annalisa
Chayka, Olesya
Pistoia, Vito
Ponzoni, Mirco
Sala, Arturo
Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
title Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
title_full Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
title_fullStr Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
title_full_unstemmed Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
title_short Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
title_sort frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282103/
https://www.ncbi.nlm.nih.gov/pubmed/22249030
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