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RESEARCH PRODUCT
High levels of HIF-2α highlight an immature neural crest-like neuroblastoma cell cohort located in a perivascular niche
Siv BeckmanIngrid ØRaRosa NogueraDavid GisselssonSven PåhlmanSamuel NavarroAlexander Pietrassubject
Vascular Endothelial Growth Factor APathologymedicine.medical_specialtySympathetic Nervous SystemAngiogenesisVimentinPathology and Forensic MedicineNeuroblastomaNeuroblastomaBasic Helix-Loop-Helix Transcription FactorsTumor Cells CulturedmedicineHumansMacrophageProgenitorOncogene ProteinsN-Myc Proto-Oncogene ProteinNeovascularization PathologicbiologyMacrophagesNuclear ProteinsNeural crestmedicine.diseasePhenotypeCell HypoxiaNeoplasm ProteinsNeural CrestNeoplastic Stem Cellsbiology.proteinCancer researchStem celldescription
High HIF-2alpha 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-2alpha-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-2alpha- and CD68-positive tumour-associated macrophages were frequently found close to the immature and HIF-2alpha-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 (c) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. (Less)
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-12-11 | The Journal of Pathology |