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Title: Frizzled receptor 6 marks rare, highly tumourigenic stem-like cells in mouse and human neuroblastomas
Authors: Cantilena, S
Pastorino, F
Pezzolo, A
Chayka, O
Pistoia, V
Ponzoni, M
Sala, A
Keywords: HIF;Hypoxia;Metastasis;Neuroblastoma;Stem cell
Issue Date: 2011
Publisher: Impact Journals
Citation: Oncotarget, 2(12): 976 - 983, Dec 2011
Abstract: 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 noncanonical 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.
Description: Copyright © 2011 Cantilena et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel Open Access Publishing Fund.
ISSN: 1949-2553
Appears in Collections:Biological Sciences
Brunel OA Publishing Fund
Dept of Life Sciences Research Papers

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