Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters

Abstract The cellular interaction with the extracellular matrix (ECM) modulates many key processes such as proliferation, migration, differentiation and survival. In addition, cells cultured under 3D conditions in presence of an ECM display a marked radioresistance towards ionizing radiation (IR) in...

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Autores principales:	Laura Babel, Miriam Grunewald, Robert Lehn, Markus Langhans, Tobias Meckel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2d8d543f15cf44068dd3f9191096d261
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spelling	oai:doaj.org-article:2d8d543f15cf44068dd3f9191096d2612021-12-02T16:06:46ZDirect evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters10.1038/s41598-017-03414-42045-2322https://doaj.org/article/2d8d543f15cf44068dd3f9191096d2612017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03414-4https://doaj.org/toc/2045-2322Abstract The cellular interaction with the extracellular matrix (ECM) modulates many key processes such as proliferation, migration, differentiation and survival. In addition, cells cultured under 3D conditions in presence of an ECM display a marked radioresistance towards ionizing radiation (IR) in comparison to conventionally 2D cultured cells. This process, also known as “cell-adhesion-mediated-radio-resistance” (CAM-RR), has been linked to the chromatin structure that differs between cells cultured on stiff surfaces versus cell grown on soft planar supports or in 3D environments. As integrins are the key mediators of cell adhesion and mechanosensing, they originate the molecular signalling towards chromatin remodelling in response to a cell’s microenvironment. We aimed to investigate this molecular origin that leads to CAM-RR by investigating the distribution of integrins at the single molecule level and show that cells cultured in 2D keep a lower fraction of integrin β1 in clusters and maintain a less defined cluster status than 3D cultured cells. Upon X-irradiation this nanoscale distribution of integrin β1 is disturbed at much lower dosages in 2D versus 3D cultured cells. Radioresistance is thus linked to the ability to maintain a well defined organization of integrins in clusters, making integrin distribution a potential drug target for radiosensitization.Laura BabelMiriam GrunewaldRobert LehnMarkus LanghansTobias MeckelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laura Babel Miriam Grunewald Robert Lehn Markus Langhans Tobias Meckel Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters
description	Abstract The cellular interaction with the extracellular matrix (ECM) modulates many key processes such as proliferation, migration, differentiation and survival. In addition, cells cultured under 3D conditions in presence of an ECM display a marked radioresistance towards ionizing radiation (IR) in comparison to conventionally 2D cultured cells. This process, also known as “cell-adhesion-mediated-radio-resistance” (CAM-RR), has been linked to the chromatin structure that differs between cells cultured on stiff surfaces versus cell grown on soft planar supports or in 3D environments. As integrins are the key mediators of cell adhesion and mechanosensing, they originate the molecular signalling towards chromatin remodelling in response to a cell’s microenvironment. We aimed to investigate this molecular origin that leads to CAM-RR by investigating the distribution of integrins at the single molecule level and show that cells cultured in 2D keep a lower fraction of integrin β1 in clusters and maintain a less defined cluster status than 3D cultured cells. Upon X-irradiation this nanoscale distribution of integrin β1 is disturbed at much lower dosages in 2D versus 3D cultured cells. Radioresistance is thus linked to the ability to maintain a well defined organization of integrins in clusters, making integrin distribution a potential drug target for radiosensitization.
format	article
author	Laura Babel Miriam Grunewald Robert Lehn Markus Langhans Tobias Meckel
author_facet	Laura Babel Miriam Grunewald Robert Lehn Markus Langhans Tobias Meckel
author_sort	Laura Babel
title	Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters
title_short	Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters
title_full	Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters
title_fullStr	Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters
title_full_unstemmed	Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters
title_sort	direct evidence for cell adhesion-mediated radioresistance (cam-rr) on the level of individual integrin β1 clusters
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2d8d543f15cf44068dd3f9191096d261
work_keys_str_mv	AT laurababel directevidenceforcelladhesionmediatedradioresistancecamrronthelevelofindividualintegrinb1clusters AT miriamgrunewald directevidenceforcelladhesionmediatedradioresistancecamrronthelevelofindividualintegrinb1clusters AT robertlehn directevidenceforcelladhesionmediatedradioresistancecamrronthelevelofindividualintegrinb1clusters AT markuslanghans directevidenceforcelladhesionmediatedradioresistancecamrronthelevelofindividualintegrinb1clusters AT tobiasmeckel directevidenceforcelladhesionmediatedradioresistancecamrronthelevelofindividualintegrinb1clusters
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Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters

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