High levels of HIF‐2α highlight an immature neural crest‐like neuroblastoma cell cohort located in a perivascular niche
Abstract
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.
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HIF-2α is co-expressed with putative CSC markers in neuroblastoma and glioblastoma.
“HIF-2α is co-expressed with putative CSC markers in neuroblastoma and glioblastoma (Pietras et al., 2008;Li et al., 2009).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Pietras et al., 2008
The tumorigenesis of pheochromocytomas, paragangliomas, and neuroblastomas seems to involve aberrant HIF-2 signaling, resulting in pseudohypoxic phenotypes linked to disseminated disease.
“Interestingly, the tumorigenesis of these closely related tumors seems to involve aberrant HIF-2 signaling, resulting in pseudohypoxic phenotypes linked to disseminated disease (Eisenhofer et al., 2004;Pietras et al., 2008;Favier et al., 2009).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Pietras et al., 2008
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References 21 · Cited by 116
- Authors
- Pietras, A., Gisselsson, D., Øra, I., Noguera, R., Beckman, S., Navarro, S., & Påhlman, S.
- Affiliations
- Lund University (SE)
- Universitat de València (ES)
- Corresponding author
- Påhlman, S
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2008-01-14
- Volume
- 214
- Issue
- 4
- Pages
- 482-488
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2017654880
- Cited by
- 116
- References
- 21
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 8 · 2022: 1 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 12 · 2014: 4 · 2013: 11 · 2012: 10
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Cancerfonden
- Gunnar Nilssons Cancerstiftelse
- Malmö Högskola
- Topics
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- neuroblastoma, HIF-2α, neural crest-like cells, perivascular niche, tumour-associated macrophages, MYCN amplification, Notch signaling, CD117, vascular endothelial growth factor, angiogenesis, tumor microenvironment, childhood cancer
- MeSH terms
- N-Myc Proto-Oncogene Protein, Endothelial PAS Domain-Containing Protein 1, Humans, Macrophages, Neoplasm Proteins, Neovascularization, Pathologic, Neural Crest, Neuroblastoma, Nuclear Proteins, Sympathetic Nervous System, Tumor Cells, Cultured, Neoplastic Stem Cells, Oncogene Proteins, Cell Hypoxia, Vascular Endothelial Growth Factor A, Basic Helix-Loop-Helix Proteins
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