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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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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 |
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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 |
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