Intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells.
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. Intermitte...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3281893?pdf=render |
| _version_ | 1818475678358568960 |
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| author | Vasantha Kumar Bhaskara Indra Mohanam Jasti S Rao Sanjeeva Mohanam |
| author_facet | Vasantha Kumar Bhaskara Indra Mohanam Jasti S Rao Sanjeeva Mohanam |
| author_sort | Vasantha Kumar Bhaskara |
| collection | DOAJ |
| description | 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.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.Our results suggest that intermittent hypoxia enhances stem-like characteristics and suppresses differentiation propensities in neuroblastoma cells. |
| first_indexed | 2024-12-10T09:15:48Z |
| format | Article |
| id | doaj.art-a33070584ebc437c9f420dd84e826181 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T09:15:48Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a33070584ebc437c9f420dd84e8261812022-12-22T01:54:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3090510.1371/journal.pone.0030905Intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells.Vasantha Kumar BhaskaraIndra MohanamJasti S RaoSanjeeva MohanamNeuroblastomas 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.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.Our results suggest that intermittent hypoxia enhances stem-like characteristics and suppresses differentiation propensities in neuroblastoma cells.http://europepmc.org/articles/PMC3281893?pdf=render |
| spellingShingle | Vasantha Kumar Bhaskara Indra Mohanam Jasti S Rao Sanjeeva Mohanam Intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3281893?pdf=render |
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