Browsing by Author "Stöhr, Daniela"

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Open Access
Characterising heterogeneous TRAIL responsiveness and overcoming TRAIL resistance in multicellular tumour spheroids
(2018) Stöhr, Daniela; Scheurich, Peter (Prof. Dr.)
Open Access
Linking hyperosmotic stress and apoptotic sensitivity
(2020) Stöhr, Daniela; Rehm, Markus
How hypertonic stress induces or sensitizes to cell death signals is incompletely understood and rarely studied in cancer. Heimer et al. demonstrate that hypertonic environments neutralize the antiapoptotic Bcl‐2 family member Mcl‐1 by upregulating its antagonist Noxa. Consequently, hypertonically stressed head and neck squamous cell carcinoma cells rely solely on Bcl‐xL for survival and succumb to apoptosis when challenged by pharmacological Bcl‐xL inhibition. Similar findings were reported in colorectal cancer cells in related manuscripts, suggesting that a common and conserved mechanistic link might exist between hyperosmotic stress and cellular sensitisation to apoptosis.
Open Access
Multiphasic modelling and computation of metastatic lung-cancer cell proliferation and atrophy in brain tissue based on experimental data
(2021) Ehlers, Wolfgang; Rehm, Markus; Schröder, Patrick; Stöhr, Daniela; Wagner, Arndt
Cancer is one of the most serious diseases for human beings, especially when metastases come into play. In the present article, the example of lung-cancer metastases in the brain is used to discuss the basic problem of cancer growth and atrophy as a result of both nutrients and medication. As the brain itself is a soft tissue that is saturated by blood and interstitial fluid, the biomechanical description of the problem is based on the Theory of Porous Media enhanced by the results of medication tests carried out in in-vitro experiments on cancer-cell cultures. Based on theoretical and experimental results, the consideration of proliferation, necrosis and apoptosis of metastatic cancer cells is included in the description by so-called mass-production terms added to the mass balances of the brain skeleton and the interstitial fluid. Furthermore, the mass interaction of nutrients and medical drugs between the solid and the interstitial fluid and its influence on proliferation, necrosis and apoptosis of cancer cells are considered. As a result, the overall model is appropriate for the description of brain tumour treatment combined with stress and deformation induced by cancer growth in the skull.
Open Access
Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids
(2020) Stöhr, Daniela; Schmid, Jens O.; Beigl, Tobias B.; Mack, Alexandra; Maichl, Daniela S.; Cao, Kai; Budai, Beate; Fullstone, Gavin; Kontermann, Roland E.; Mürdter, Thomas E.; Tait, Stephen W. G.; Hagenlocher, Cathrin; Pollak, Nadine; Scheurich, Peter; Rehm, Markus
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.