PloS one, 2012-02, Vol.7 (2), p.e30905
2012
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- Autor(en) / Beteiligte
- Titel
- Intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells
- Ist Teil von
- PloS one, 2012-02, Vol.7 (2), p.e30905
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0030905Titel-ID: cdi_plos_journals_1323567315
- Format
- –
- Schlagworte
- Acids, Analysis, Biology, Biomarkers, Tumor - metabolism, Bone marrow, Cancer therapies, Cell culture, Cell differentiation, Cell Differentiation - drug effects, Cell Differentiation - genetics, Cell Hypoxia - drug effects, Cell Line, Tumor, Cell survival, Cell Survival - genetics, Chemotherapy, Children, Children & youth, Conditioning, Differentiation (biology), Gene Expression Regulation, Neoplastic - drug effects, Gene Knockdown Techniques, Genes, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Immunofluorescence, Immunoglobulins, Malignancy, Markers, Medical prognosis, Medicine, Morphology, Neoplastic Stem Cells - drug effects, Neoplastic Stem Cells - metabolism, Neoplastic Stem Cells - pathology, Neural crest, Neural Crest - metabolism, Neural stem cells, Neuroblastoma, Neuroblastoma - genetics, Neuroblastoma - pathology, Neuroblastoma cells, Oxygenation, Pharmacology, Proteins, Radiation therapy, Real time, Retinoic acid, RNA, Small Interfering - metabolism, Rodents, Solid tumors, Stem cells, Sympathetic nervous system, Sympathetic Nervous System - metabolism, Tretinoin - pharmacology, Tumors, Western blotting