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Open AccessArticle

Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

1
Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
2
Department of Biomedicine, Aarhus University, Hoegh-Guldbergsgade 10, 8000 Aarhus C, Denmark
3
Department of Ophthalmology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark
4
Research Group “Magdeburger Arbeitsgemeinschaft für Forschung unter Raumfahrt- und Schwerelosigkeitsbedingungen” (MARS), Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany
5
Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke University, Pfälzer Platz, 39106 Magdeburg, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 367; https://doi.org/10.3390/cells9020367
Received: 9 December 2019 / Revised: 31 January 2020 / Accepted: 4 February 2020 / Published: 5 February 2020
(This article belongs to the Special Issue Killing Cancer: Discovery and Selection of New Target Molecules)
Detachment and the formation of spheroids under microgravity conditions can be observed with various types of intrinsically adherent human cells. In particular, for cancer cells this process mimics metastasis and may provide insights into cancer biology and progression that can be used to identify new drug/target combinations for future therapies. By using the synthetic glucocorticoid dexamethasone (DEX), we were able to suppress spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells that were exposed to altered gravity conditions on a random positioning machine. DEX inhibited the growth of three-dimensional cell aggregates in a dose-dependent manner. In the first approach, we analyzed the expression of several factors that are known to be involved in key processes of cancer progression such as autocrine signaling, proliferation, epithelial–mesenchymal transition, and anoikis. Wnt/β-catenin signaling and expression patterns of important genes in cancer cell growth and survival, which were further suggested to play a role in three-dimensional aggregation, such as NFKB2, VEGFA, CTGF, CAV1, BCL2(L1), or SNAI1, were clearly affected by DEX. Our data suggest the presence of a more complex regulation network of tumor spheroid formation involving additional signal pathways or individual key players that are also influenced by DEX.
Keywords: glucocorticoids; 3D growth; nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB); epithelial–mesenchymal transition; anoikis; proliferation glucocorticoids; 3D growth; nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB); epithelial–mesenchymal transition; anoikis; proliferation
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Melnik, D.; Sahana, J.; Corydon, T.J.; Kopp, S.; Nassef, M.Z.; Wehland, M.; Infanger, M.; Grimm, D.; Krüger, M. Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity. Cells 2020, 9, 367.

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