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Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells
BACKGROUND: Neuroblastoma is the most common extracranial solid tumor of childhood. The heterogeneous microenvironment of solid tumors contains hypoxic regions associated with poor prognosis and chemoresistance. Hypoxia implicates the actin cytoskeleton through its essential roles in motility, invas...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608101/ https://www.ncbi.nlm.nih.gov/pubmed/26475688 http://dx.doi.org/10.1186/s12885-015-1741-8 |
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author | Glass, Joshua J. Phillips, Phoebe A. Gunning, Peter W. Stehn, Justine R. |
author_facet | Glass, Joshua J. Phillips, Phoebe A. Gunning, Peter W. Stehn, Justine R. |
author_sort | Glass, Joshua J. |
collection | PubMed |
description | BACKGROUND: Neuroblastoma is the most common extracranial solid tumor of childhood. The heterogeneous microenvironment of solid tumors contains hypoxic regions associated with poor prognosis and chemoresistance. Hypoxia implicates the actin cytoskeleton through its essential roles in motility, invasion and proliferation. However, hypoxia-induced changes in the actin cytoskeleton have only recently been observed in human cells. Tropomyosins are key regulators of the actin cytoskeleton and we hypothesized that tropomyosins may mediate hypoxic phenotypes. METHODS: Neuroblastoma (SH-EP) cells were incubated ± hypoxia (1 % O(2), 5 % CO(2)) for up to 144 h, before examining the cytoskeleton by confocal microscopy and Western blotting. RESULTS: Hypoxic cells were characterized by a more organized actin cytoskeleton and a reduced ability to degrade gelatin substrates. Hypoxia significantly increased mean actin filament bundle width (72 h) and actin filament length (72–96 h). This correlated with increased hypoxic expression and filamentous organization of stabilizing tropomyosins Tm1 and Tm2. However, isoform specific changes in tropomyosin expression were more evident at 96 h. CONCLUSIONS: This study demonstrates hypoxia-induced changes in the recruitment of high molecular weight tropomyosins into the actin stress fibres of a human cancer. While hypoxia induced clear changes in actin organization compared with parallel normoxic cultures of neuroblastoma, the precise role of tropomyosins in this hypoxic actin reorganization remains to be determined. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1741-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4608101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46081012015-10-17 Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells Glass, Joshua J. Phillips, Phoebe A. Gunning, Peter W. Stehn, Justine R. BMC Cancer Research Article BACKGROUND: Neuroblastoma is the most common extracranial solid tumor of childhood. The heterogeneous microenvironment of solid tumors contains hypoxic regions associated with poor prognosis and chemoresistance. Hypoxia implicates the actin cytoskeleton through its essential roles in motility, invasion and proliferation. However, hypoxia-induced changes in the actin cytoskeleton have only recently been observed in human cells. Tropomyosins are key regulators of the actin cytoskeleton and we hypothesized that tropomyosins may mediate hypoxic phenotypes. METHODS: Neuroblastoma (SH-EP) cells were incubated ± hypoxia (1 % O(2), 5 % CO(2)) for up to 144 h, before examining the cytoskeleton by confocal microscopy and Western blotting. RESULTS: Hypoxic cells were characterized by a more organized actin cytoskeleton and a reduced ability to degrade gelatin substrates. Hypoxia significantly increased mean actin filament bundle width (72 h) and actin filament length (72–96 h). This correlated with increased hypoxic expression and filamentous organization of stabilizing tropomyosins Tm1 and Tm2. However, isoform specific changes in tropomyosin expression were more evident at 96 h. CONCLUSIONS: This study demonstrates hypoxia-induced changes in the recruitment of high molecular weight tropomyosins into the actin stress fibres of a human cancer. While hypoxia induced clear changes in actin organization compared with parallel normoxic cultures of neuroblastoma, the precise role of tropomyosins in this hypoxic actin reorganization remains to be determined. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1741-8) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-16 /pmc/articles/PMC4608101/ /pubmed/26475688 http://dx.doi.org/10.1186/s12885-015-1741-8 Text en © Glass et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Glass, Joshua J. Phillips, Phoebe A. Gunning, Peter W. Stehn, Justine R. Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells |
title | Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells |
title_full | Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells |
title_fullStr | Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells |
title_full_unstemmed | Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells |
title_short | Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells |
title_sort | hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608101/ https://www.ncbi.nlm.nih.gov/pubmed/26475688 http://dx.doi.org/10.1186/s12885-015-1741-8 |
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