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...

Full description

Saved in:
Bibliographic Details
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.2304