Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids
| العنوان: | Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids |
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| المؤلفون: | Kai Cao, Peter Scheurich, Roland E. Kontermann, Tobias B. Beigl, Thomas E. Mürdter, Cathrin Hagenlocher, Alexandra Mack, Daniela Simone Maichl, Stephen W.G. Tait, Daniela Stöhr, Markus Rehm, Beate Budai, Jens O Schmid, Gavin Fullstone, Nadine Pollak |
| المصدر: | Cell Death and Differentiation |
| بيانات النشر: | Springer Nature, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer microenvironment, Tumour heterogeneity, Cell, Apoptosis, Article, TNF-Related Apoptosis-Inducing Ligand, Cell Line, Tumor, Neoplasms, Spheroids, Cellular, medicine, Humans, Molecular Biology, Cyclooxygenase 2 Inhibitors, Chemistry, Spheroid, Cell Biology, Ligand (biochemistry), Cell biology, Receptors, TNF-Related Apoptosis-Inducing Ligand, medicine.anatomical_structure, Celecoxib, Drug Resistance, Neoplasm, Cancer cell, embryonic structures, Unfolded protein response, Tumor necrosis factor alpha, Trail resistance |
| الوصف: | The 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. Deutsche Forschungsgemeinschaft (German Research Foundation) European Union’s Horizon 2020 research and innovation program Cluster of Excellence in Simulation Technology Projekt DEAL |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1350-9047 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4746167a42442d4aa67874014f1dcaf8 https://eprints.gla.ac.uk/219472/1/219472.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4746167a42442d4aa67874014f1dcaf8 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 13509047 |
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