The HIF-2alpha-Driven Pseudo-Hypoxic Phenotype in Tumor Aggressiveness, Differentiation, and Vascularization.
Pietras, Alexander LU ; Mohlin, Sofie LU
and Påhlman, Sven
LU
(2010)
In Current Topics in Microbiology and Immunology
345.
p.1-20
- Abstract
- Cellular adaptation to diminished tissue oxygen tensions, hypoxia, is largely governed by the hypoxia inducible transcription factors, HIF-1 and HIF-2. Tumor hypoxia and high HIF protein levels are frequently associated with aggressive disease. In recent years, high tumor cell levels of HIF-2 and the oxygen sensitive subunit HIF-2alpha have been associated with unfavorable disease and shown to be highly expressed in tumor stem/initiating cells originating from neuroblastoma and glioma, respectively. In these cells, HIF-2 is active under nonhypoxic conditions as well, creating a pseudo-hypoxic phenotype with clear influence on tumor behavior. Neuroblastoma tumor initiating cells are immature with a neural crest-like phenotype and... (More)
- Cellular adaptation to diminished tissue oxygen tensions, hypoxia, is largely governed by the hypoxia inducible transcription factors, HIF-1 and HIF-2. Tumor hypoxia and high HIF protein levels are frequently associated with aggressive disease. In recent years, high tumor cell levels of HIF-2 and the oxygen sensitive subunit HIF-2alpha have been associated with unfavorable disease and shown to be highly expressed in tumor stem/initiating cells originating from neuroblastoma and glioma, respectively. In these cells, HIF-2 is active under nonhypoxic conditions as well, creating a pseudo-hypoxic phenotype with clear influence on tumor behavior. Neuroblastoma tumor initiating cells are immature with a neural crest-like phenotype and downregulation of HIF-2alpha in these cells results in neuronal sympathetic differentiation and the cells become phenotypically similar to the bulk of neuroblastoma cells found in clinical specimens. Knockdown of HIF-2alpha in neuroblastoma and glioma tumor stem/initiating cells leads to reduced levels of VEGF and poorly vascularized, highly necrotic tumors. As high HIF-2alpha expression further correlates with disseminated disease as demonstrated in neuroblastoma, glioma, and breast carcinoma, we propose that targeting HIF-2alpha and/or the pseudo-hypoxic phenotype induced by HIF-2 under normoxic conditions has great clinical potential. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1626456
- author
- Pietras, Alexander
LU
; Mohlin, Sofie
LU
and Påhlman, Sven
LU
- organization
- publishing date
- 2010
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- host publication
- Diverse Effects of Hypoxia on Tumor Progression
- series title
- Current Topics in Microbiology and Immunology
- editor
- Celeste Simon, M.
- volume
- 345
- pages
- 1 - 20
- publisher
- Springer
- external identifiers
-
- wos:000282105100001
- pmid:20517717
- pmid:20517717
- scopus:78349283042
- ISSN
- 0070-217X
- ISBN
- 978-3-642-13328-2
- 978-3-642-13329-9
- DOI
- 10.1007/82_2010_72
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine (013031200)
- id
- ecf3c49f-5038-4d94-a89d-062e1056050f (old id 1626456)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20517717?dopt=Abstract
- date added to LUP
- 2016-04-01 14:38:43
- date last changed
- 2024-02-03 07:20:10
@inbook{ecf3c49f-5038-4d94-a89d-062e1056050f,
abstract = {{Cellular adaptation to diminished tissue oxygen tensions, hypoxia, is largely governed by the hypoxia inducible transcription factors, HIF-1 and HIF-2. Tumor hypoxia and high HIF protein levels are frequently associated with aggressive disease. In recent years, high tumor cell levels of HIF-2 and the oxygen sensitive subunit HIF-2alpha have been associated with unfavorable disease and shown to be highly expressed in tumor stem/initiating cells originating from neuroblastoma and glioma, respectively. In these cells, HIF-2 is active under nonhypoxic conditions as well, creating a pseudo-hypoxic phenotype with clear influence on tumor behavior. Neuroblastoma tumor initiating cells are immature with a neural crest-like phenotype and downregulation of HIF-2alpha in these cells results in neuronal sympathetic differentiation and the cells become phenotypically similar to the bulk of neuroblastoma cells found in clinical specimens. Knockdown of HIF-2alpha in neuroblastoma and glioma tumor stem/initiating cells leads to reduced levels of VEGF and poorly vascularized, highly necrotic tumors. As high HIF-2alpha expression further correlates with disseminated disease as demonstrated in neuroblastoma, glioma, and breast carcinoma, we propose that targeting HIF-2alpha and/or the pseudo-hypoxic phenotype induced by HIF-2 under normoxic conditions has great clinical potential.}},
author = {{Pietras, Alexander and Mohlin, Sofie and Påhlman, Sven}},
booktitle = {{Diverse Effects of Hypoxia on Tumor Progression}},
editor = {{Celeste Simon, M.}},
isbn = {{978-3-642-13328-2}},
issn = {{0070-217X}},
language = {{eng}},
pages = {{1--20}},
publisher = {{Springer}},
series = {{Current Topics in Microbiology and Immunology}},
title = {{The HIF-2alpha-Driven Pseudo-Hypoxic Phenotype in Tumor Aggressiveness, Differentiation, and Vascularization.}},
url = {{https://lup.lub.lu.se/search/files/18561391/1653282.pdf}},
doi = {{10.1007/82_2010_72}},
volume = {{345}},
year = {{2010}},
}