Cargando…

Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia

Hypoxia is one of the most important features of the tumor microenvironment, exerting an adverse effect on tumor aggressiveness and patient prognosis. Two types of hypoxia may occur within the tumor mass, chronic (prolonged) and cycling (transient, intermittent) hypoxia. Cycling hypoxia has been sho...

Descripción completa

Detalles Bibliográficos
Autores principales: Olbryt, Magdalena, Habryka, Anna, Student, Sebastian, Jarząb, Michał, Tyszkiewicz, Tomasz, Lisowska, Katarzyna Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133353/
https://www.ncbi.nlm.nih.gov/pubmed/25122487
http://dx.doi.org/10.1371/journal.pone.0105104
_version_ 1782330747344912384
author Olbryt, Magdalena
Habryka, Anna
Student, Sebastian
Jarząb, Michał
Tyszkiewicz, Tomasz
Lisowska, Katarzyna Marta
author_facet Olbryt, Magdalena
Habryka, Anna
Student, Sebastian
Jarząb, Michał
Tyszkiewicz, Tomasz
Lisowska, Katarzyna Marta
author_sort Olbryt, Magdalena
collection PubMed
description Hypoxia is one of the most important features of the tumor microenvironment, exerting an adverse effect on tumor aggressiveness and patient prognosis. Two types of hypoxia may occur within the tumor mass, chronic (prolonged) and cycling (transient, intermittent) hypoxia. Cycling hypoxia has been shown to induce aggressive tumor cell phenotype and radioresistance more significantly than chronic hypoxia, though little is known about the molecular mechanisms underlying this phenomenon. The aim of this study was to delineate the molecular response to both types of hypoxia induced experimentally in tumor cells, with a focus on cycling hypoxia. We analyzed in vitro gene expression profile in three human cancer cell lines (melanoma, ovarian cancer, and prostate cancer) exposed to experimental chronic or transient hypoxia conditions. As expected, the cell-type specific variability in response to hypoxia was significant. However, the expression of 240 probe sets was altered in all 3 cell lines. We found that gene expression profiles induced by both types of hypoxia were qualitatively similar and strongly depend on the cell type. Cycling hypoxia altered the expression of fewer genes than chronic hypoxia (6,132 vs. 8,635 probe sets, FDR adjusted p<0.05), and with lower fold changes. However, the expression of some of these genes was significantly more affected by cycling hypoxia than by prolonged hypoxia, such as IL8, PLAU, and epidermal growth factor (EGF) pathway-related genes (AREG, HBEGF, and EPHA2). These transcripts were, in most cases, validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our results indicate that experimental cycling hypoxia exerts similar, although less intense effects, on the examined cancer cell lines than its chronic counterpart. Nonetheless, we identified genes and molecular pathways that seem to be preferentially regulated by cyclic hypoxia.
format Online
Article
Text
id pubmed-4133353
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-41333532014-08-19 Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia Olbryt, Magdalena Habryka, Anna Student, Sebastian Jarząb, Michał Tyszkiewicz, Tomasz Lisowska, Katarzyna Marta PLoS One Research Article Hypoxia is one of the most important features of the tumor microenvironment, exerting an adverse effect on tumor aggressiveness and patient prognosis. Two types of hypoxia may occur within the tumor mass, chronic (prolonged) and cycling (transient, intermittent) hypoxia. Cycling hypoxia has been shown to induce aggressive tumor cell phenotype and radioresistance more significantly than chronic hypoxia, though little is known about the molecular mechanisms underlying this phenomenon. The aim of this study was to delineate the molecular response to both types of hypoxia induced experimentally in tumor cells, with a focus on cycling hypoxia. We analyzed in vitro gene expression profile in three human cancer cell lines (melanoma, ovarian cancer, and prostate cancer) exposed to experimental chronic or transient hypoxia conditions. As expected, the cell-type specific variability in response to hypoxia was significant. However, the expression of 240 probe sets was altered in all 3 cell lines. We found that gene expression profiles induced by both types of hypoxia were qualitatively similar and strongly depend on the cell type. Cycling hypoxia altered the expression of fewer genes than chronic hypoxia (6,132 vs. 8,635 probe sets, FDR adjusted p<0.05), and with lower fold changes. However, the expression of some of these genes was significantly more affected by cycling hypoxia than by prolonged hypoxia, such as IL8, PLAU, and epidermal growth factor (EGF) pathway-related genes (AREG, HBEGF, and EPHA2). These transcripts were, in most cases, validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our results indicate that experimental cycling hypoxia exerts similar, although less intense effects, on the examined cancer cell lines than its chronic counterpart. Nonetheless, we identified genes and molecular pathways that seem to be preferentially regulated by cyclic hypoxia. Public Library of Science 2014-08-14 /pmc/articles/PMC4133353/ /pubmed/25122487 http://dx.doi.org/10.1371/journal.pone.0105104 Text en © 2014 Olbryt 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
Olbryt, Magdalena
Habryka, Anna
Student, Sebastian
Jarząb, Michał
Tyszkiewicz, Tomasz
Lisowska, Katarzyna Marta
Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia
title Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia
title_full Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia
title_fullStr Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia
title_full_unstemmed Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia
title_short Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia
title_sort global gene expression profiling in three tumor cell lines subjected to experimental cycling and chronic hypoxia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133353/
https://www.ncbi.nlm.nih.gov/pubmed/25122487
http://dx.doi.org/10.1371/journal.pone.0105104
work_keys_str_mv AT olbrytmagdalena globalgeneexpressionprofilinginthreetumorcelllinessubjectedtoexperimentalcyclingandchronichypoxia
AT habrykaanna globalgeneexpressionprofilinginthreetumorcelllinessubjectedtoexperimentalcyclingandchronichypoxia
AT studentsebastian globalgeneexpressionprofilinginthreetumorcelllinessubjectedtoexperimentalcyclingandchronichypoxia
AT jarzabmichał globalgeneexpressionprofilinginthreetumorcelllinessubjectedtoexperimentalcyclingandchronichypoxia
AT tyszkiewicztomasz globalgeneexpressionprofilinginthreetumorcelllinessubjectedtoexperimentalcyclingandchronichypoxia
AT lisowskakatarzynamarta globalgeneexpressionprofilinginthreetumorcelllinessubjectedtoexperimentalcyclingandchronichypoxia