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dc.contributor.authorStöhr, Daniela-
dc.contributor.authorSchmid, Jens O.-
dc.contributor.authorBeigl, Tobias B.-
dc.contributor.authorMack, Alexandra-
dc.contributor.authorMaichl, Daniela S.-
dc.contributor.authorCao, Kai-
dc.contributor.authorBudai, Beate-
dc.contributor.authorFullstone, Gavin-
dc.contributor.authorKontermann, Roland E.-
dc.contributor.authorMürdter, Thomas E.-
dc.contributor.authorTait, Stephen W. G.-
dc.contributor.authorHagenlocher, Cathrin-
dc.contributor.authorPollak, Nadine-
dc.contributor.authorScheurich, Peter-
dc.contributor.authorRehm, Markus-
dc.date.accessioned2023-06-27T12:52:05Z-
dc.date.available2023-06-27T12:52:05Z-
dc.date.issued2020de
dc.identifier.issn1350-9047-
dc.identifier.issn1476-5403-
dc.identifier.other1852604395-
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-132614de
dc.identifier.urihttp://elib.uni-stuttgart.de/handle/11682/13261-
dc.identifier.urihttp://dx.doi.org/10.18419/opus-13242-
dc.description.abstractThe influence of 3D microenvironments on apoptosis susceptibility remains poorly understood. Here, we studied the susceptibility of cancer cell spheroids, grown to the size of micrometastases, to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Interestingly, pronounced, spatially coordinated response heterogeneities manifest within spheroidal microenvironments: In spheroids grown from genetically identical cells, TRAIL-resistant subpopulations enclose, and protect TRAIL-hypersensitive cells, thereby increasing overall treatment resistance. TRAIL-resistant layers form at the interface of proliferating and quiescent cells and lack both TRAILR1 and TRAILR2 protein expression. In contrast, oxygen, and nutrient deprivation promote high amounts of TRAILR2 expression in TRAIL-hypersensitive cells in inner spheroid layers. COX-II inhibitor celecoxib further enhanced TRAILR2 expression in spheroids, likely resulting from increased ER stress, and thereby re-sensitized TRAIL-resistant cell layers to treatment. Our analyses explain how TRAIL response heterogeneities manifest within well-defined multicellular environments, and how spatial barriers of TRAIL resistance can be minimized and eliminated.en
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (German Research Foundation)de
dc.description.sponsorshipEuropean Union’s Horizon 2020 research and innovation programde
dc.description.sponsorshipCluster of Excellence in Simulation Technologyde
dc.description.sponsorshipProjekt DEALde
dc.language.isoende
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/675448de
dc.relation.uridoi:10.1038/s41418-020-0559-3de
dc.rightsinfo:eu-repo/semantics/openAccessde
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/de
dc.subject.ddc570de
dc.subject.ddc610de
dc.titleStress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroidsen
dc.typearticlede
dc.date.updated2023-05-16T02:23:25Z-
ubs.fakultaetEnergie-, Verfahrens- und Biotechnikde
ubs.fakultaetFakultäts- und hochschulübergreifende Einrichtungende
ubs.fakultaetFakultätsübergreifend / Sonstige Einrichtungde
ubs.institutInstitut für Zellbiologie und Immunologiede
ubs.institutStuttgart Research Center Systems Biology (SRCSB)de
ubs.institutFakultätsübergreifend / Sonstige Einrichtungde
ubs.publikation.seiten3037-3052de
ubs.publikation.sourceCell death & differentiation 27 (2020), S. 3037-3052de
ubs.publikation.typZeitschriftenartikelde
Enthalten in den Sammlungen:04 Fakultät Energie-, Verfahrens- und Biotechnik

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