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Published on: December 17, 2017
Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity
Daniela Melnik1, Jayashree Sahana2, Thomas J Corydon2,3
1Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
Abstract:
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.
Insights
Dexamethasone (DEX) suppressed follicular thyroid cancer cell spheroid formation in microgravity. DEX impacted key cancer progression genes, suggesting complex regulation of tumor growth and potential therapeutic targets.
Area of Science:
- Cell Biology
- Cancer Research
- Gravitational Biology
Background:
- Tumor spheroid formation under microgravity mimics metastasis in cancer.
- Understanding this process can reveal new therapeutic targets for cancer progression.
Purpose of the Study:
- To investigate the effect of dexamethasone (DEX) on spheroid formation in follicular thyroid cancer (FTC)-133 cells under altered gravity.
- To analyze the molecular mechanisms underlying DEX's impact on cancer cell aggregation and progression.
Main Methods:
- Follicular thyroid cancer cells (FTC-133) were cultured under altered gravity using a random positioning machine.
- Dexamethasone (DEX) was applied to assess its effect on spheroid formation.
- Gene expression analysis was performed for key cancer progression factors.
Main Results:
- DEX significantly inhibited the dose-dependent growth of three-dimensional cell aggregates (spheroids).
- DEX altered the expression of genes involved in Wnt/β-catenin signaling, autocrine signaling, proliferation, epithelial-mesenchymal transition, and anoikis.
- Key affected genes included NFKB2, VEGFA, CTGF, CAV1, BCL2(L1), and SNAI1.
Conclusions:
- Dexamethasone (DEX) effectively suppresses tumor spheroid formation in follicular thyroid cancer cells under altered gravity.
- DEX influences multiple signaling pathways critical for cancer progression, indicating a complex regulatory network.
- These findings highlight potential new therapeutic strategies targeting spheroid formation and cancer metastasis.
