Cargando…

Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells

BACKGROUND: Neuroblastomas are the most common extracranial solid tumors in children. Neuroblastomas are derived from immature cells of the sympathetic nervous system and are characterized by clinical and biological heterogeneity. Hypoxia has been linked to tumor progression and increased malignancy...

Descripción completa

Detalles Bibliográficos
Autores principales: Bhaskara, Vasantha Kumar, Mohanam, Indra, Rao, Jasti S., Mohanam, Sanjeeva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281893/
https://www.ncbi.nlm.nih.gov/pubmed/22363512
http://dx.doi.org/10.1371/journal.pone.0030905
_version_ 1782224011987517440
author Bhaskara, Vasantha Kumar
Mohanam, Indra
Rao, Jasti S.
Mohanam, Sanjeeva
author_facet Bhaskara, Vasantha Kumar
Mohanam, Indra
Rao, Jasti S.
Mohanam, Sanjeeva
author_sort Bhaskara, Vasantha Kumar
collection PubMed
description BACKGROUND: Neuroblastomas are the most common extracranial solid tumors in children. Neuroblastomas are derived from immature cells of the sympathetic nervous system and are characterized by clinical and biological heterogeneity. Hypoxia has been linked to tumor progression and increased malignancy. Intermittent hypoxia or repeated episodes of hypoxia followed by re-oxygenation is a common phenomenon in solid tumors including neuroblastoma and it has a significant influence on the outcome of therapies. The present study focuses on how intermittent hypoxia modulates the stem-like properties and differentiation in neuroblastoma cells. METHODS AND FINDINGS: Cell survival was assessed by clonogenic assay and cell differentiation was determined by morphological characterization. Hypoxia-inducible genes were analyzed by real-time PCR and Western blotting. Immunofluorescence, real-time PCR and Western blotting were utilized to study stem cell markers. Analysis of neural crest / sympathetic nervous system (SNS) markers and neuronal differentiation markers were done by real-time PCR and Western blotting, respectively. Intermittent hypoxia stimulated the levels of HIF-1α and HIF-2 α proteins and enhanced stem-like properties of neuroblastoma cells. In intermittent hypoxia-conditioned cells, downregulation of SNS marker genes and upregulation of genes expressed in the neural crest were observed. Intermittent hypoxia suppressed the retinoic acid-induced differentiation of neuroblastoma cells. CONCLUSIONS: Our results suggest that intermittent hypoxia enhances stem-like characteristics and suppresses differentiation propensities in neuroblastoma cells.
format Online
Article
Text
id pubmed-3281893
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-32818932012-02-23 Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells Bhaskara, Vasantha Kumar Mohanam, Indra Rao, Jasti S. Mohanam, Sanjeeva PLoS One Research Article BACKGROUND: Neuroblastomas are the most common extracranial solid tumors in children. Neuroblastomas are derived from immature cells of the sympathetic nervous system and are characterized by clinical and biological heterogeneity. Hypoxia has been linked to tumor progression and increased malignancy. Intermittent hypoxia or repeated episodes of hypoxia followed by re-oxygenation is a common phenomenon in solid tumors including neuroblastoma and it has a significant influence on the outcome of therapies. The present study focuses on how intermittent hypoxia modulates the stem-like properties and differentiation in neuroblastoma cells. METHODS AND FINDINGS: Cell survival was assessed by clonogenic assay and cell differentiation was determined by morphological characterization. Hypoxia-inducible genes were analyzed by real-time PCR and Western blotting. Immunofluorescence, real-time PCR and Western blotting were utilized to study stem cell markers. Analysis of neural crest / sympathetic nervous system (SNS) markers and neuronal differentiation markers were done by real-time PCR and Western blotting, respectively. Intermittent hypoxia stimulated the levels of HIF-1α and HIF-2 α proteins and enhanced stem-like properties of neuroblastoma cells. In intermittent hypoxia-conditioned cells, downregulation of SNS marker genes and upregulation of genes expressed in the neural crest were observed. Intermittent hypoxia suppressed the retinoic acid-induced differentiation of neuroblastoma cells. CONCLUSIONS: Our results suggest that intermittent hypoxia enhances stem-like characteristics and suppresses differentiation propensities in neuroblastoma cells. Public Library of Science 2012-02-17 /pmc/articles/PMC3281893/ /pubmed/22363512 http://dx.doi.org/10.1371/journal.pone.0030905 Text en Bhaskara et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bhaskara, Vasantha Kumar
Mohanam, Indra
Rao, Jasti S.
Mohanam, Sanjeeva
Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells
title Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells
title_full Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells
title_fullStr Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells
title_full_unstemmed Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells
title_short Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells
title_sort intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281893/
https://www.ncbi.nlm.nih.gov/pubmed/22363512
http://dx.doi.org/10.1371/journal.pone.0030905
work_keys_str_mv AT bhaskaravasanthakumar intermittenthypoxiaregulatesstemlikecharacteristicsanddifferentiationofneuroblastomacells
AT mohanamindra intermittenthypoxiaregulatesstemlikecharacteristicsanddifferentiationofneuroblastomacells
AT raojastis intermittenthypoxiaregulatesstemlikecharacteristicsanddifferentiationofneuroblastomacells
AT mohanamsanjeeva intermittenthypoxiaregulatesstemlikecharacteristicsanddifferentiationofneuroblastomacells