High levels of HIF-2α highlight an immature neural crest-like neuroblastoma cell cohort located in a perivascular niche

High HIF-2α protein levels in the sympathetic nervous system-derived childhood tumour neuroblastoma as well as immature phenotype correlate to unfavourable outcome. Here we show that a small subset of perivascularly located, strongly HIF-2α-positive tumour cells (MYCN amplified) lacks expression of...

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Published in:The Journal of pathology 2008-03, Vol.214 (4), p.482-488
Main Authors: Pietras, A, Gisselsson, D, Øra, I, Noguera, R, Beckman, S, Navarro, S, Påhlman, S
Format: Article
Language:English
Subjects:
HIF-2α
hypoxia
neural crest
neuroblastoma
perivascular niche
tumour stem cells
tumour-associated macrophages
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creator Pietras, A
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description High HIF-2α protein levels in the sympathetic nervous system-derived childhood tumour neuroblastoma as well as immature phenotype correlate to unfavourable outcome. Here we show that a small subset of perivascularly located, strongly HIF-2α-positive tumour cells (MYCN amplified) lacks expression of differentiation markers, but expresses neural crest and early sympathetic progenitor marker genes such as Notch-1, HES-1, c-Kit, dHAND, and vimentin. HIF-2α- and CD68-positive tumour-associated macrophages were frequently found close to the immature and HIF-2α-positive neuroblastoma cells and as VEGF levels are high in the perivascular niche, we hypothesize that neuroblastoma neural crest-like cells and macrophages cooperate to facilitate angiogenesis and thereby contribute to the aggressive neuroblastoma phenotype. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
doi_str_mv 10.1002/path.2304
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Pathol</addtitle><date>2008-03</date><risdate>2008</risdate><volume>214</volume><issue>4</issue><spage>482</spage><epage>488</epage><pages>482-488</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><notes>http://dx.doi.org/10.1002/path.2304</notes><notes>Swedish Cancer Society</notes><notes>Children's Cancer Foundation of Sweden</notes><notes>Instituto Carlos III, Madrid, Spain - No. PI06/5176; No. RD06/0020/0102</notes><notes>ArticleID:PATH2304</notes><notes>Gunnar Nilsson's Cancer Foundation</notes><notes>Swedish Research Council</notes><notes>istex:14264F1ECC8E05584AB861704820B099A7CF37DD</notes><notes>ark:/67375/WNG-V6FJ95BC-L</notes><notes>Hans von Kantzows Stiftelse</notes><notes>Malmö University Hospital</notes><notes>No conflicts of interest were declared.</notes><notes>SSF Strategic Center for Translational Cancer Research-CREATE Health</notes><abstract>High HIF-2α protein levels in the sympathetic nervous system-derived childhood tumour neuroblastoma as well as immature phenotype correlate to unfavourable outcome. 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subjects HIF-2α
hypoxia
neural crest
neuroblastoma
perivascular niche
tumour stem cells
tumour-associated macrophages
title High levels of HIF-2α highlight an immature neural crest-like neuroblastoma cell cohort located in a perivascular niche
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