Dexamethasone Selectively Inhibits Detachment of Metastatic Thyroid Cancer Cells during Random Positioning

Melnik, Daniela; Cortés-Sánchez, José Luis; Sandt, Viviann; Kahlert, Stefan; Kopp, Sascha; Grimm, Daniela; Krüger, Marcus

doi:10.3390/cancers15061641

Cited by 8 publications

(9 citation statements)

References 91 publications

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“…A new study by Melnik et al [ 185 ] demonstrated that this inhibition was selective for two metastatic thyroid cancer-cell lines, FTC-133 and WRO, whereas benign Nthy-ori 3-1 thyrocytes and recurrent ML-1 follicular thyroid cancer cells were not affected by DEX (0, 10, 100, 1000 nM) when exposed for 72 h to the RPM ( Table 9 ). DEX disrupts random positioning-triggered p38 stress signaling in FTC-133 cells [ 185 ]. DEX treatment of FTC-133 cells is associated with enhanced adhesiveness.…”

Section: Resultsmentioning

confidence: 99%

“…This process is caused by the restored, pronounced formation of a normal number of tight junctions. In addition, RPM-exposed Nthy-ori 3-1 and ML-1 cells exhibit an elevation in the anti-adhesion protein mucin-1, which might be a protection mechanism against mechanical stress [ 185 ]. The balance between adhesion, anti-adhesion, and cell–cell connections enables the detachment of adherent human cells exposed to the RPM or not, allowing selective inhibition of thyroid in vitro metastasis by DEX [ 185 ].…”

Section: Resultsmentioning

confidence: 99%

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Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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Microgravity (µg) has a massive impact on the health of space explorers. Microgravity changes the proliferation, differentiation, and growth of cells. As crewed spaceflights into deep space are being planned along with the commercialization of space travelling, researchers have focused on gene regulation in cells and organisms exposed to real (r-) and simulated (s-) µg. In particular, cancer and metastasis research benefits from the findings obtained under µg conditions. Gene regulation is a key factor in a cell or an organism’s ability to sustain life and respond to environmental changes. It is a universal process to control the amount, location, and timing in which genes are expressed. In this review, we provide an overview of µg-induced changes in the numerous mechanisms involved in gene regulation, including regulatory proteins, microRNAs, and the chemical modification of DNA. In particular, we discuss the current knowledge about the impact of microgravity on gene regulation in different types of bacteria, protists, fungi, animals, humans, and cells with a focus on the brain, eye, endothelium, immune system, cartilage, muscle, bone, and various cancers as well as recent findings in plants. Importantly, the obtained data clearly imply that µg experiments can support translational medicine on Earth.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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“…Melnik et al [ 23 ] used a random-positioning-based metastasis model [ 24 ] to study the inhibitory effects of dexamethasone in more detail. The team of authors demonstrated that mechanical stress plays an important role in this in vitro model with follicular thyroid carcinoma (FTC) cells and that tumor cells not derived from metastases respond differently to this stress when compared to healthy or recurrent cells.…”

Section: Updates On Models Mimicking Physiological Processesmentioning

confidence: 99%

Tumor Models and Drug Targeting In Vitro—Where Are We Today? Where Do We Go from Here?

Krüger

Kopp

2023

Cancers

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“…The procedure was performed in the same way as described in [18]. To obtain sufficient mRNA out of the cells grown in channel slides, a higher cell number of 40,000 cells/cm 2 and a µ-Slide, 0.8 Luer, ibiTreat (ibidi) were used.…”

Section: Mrna Isolation and Quantitative Real-time Pcr (Ftc-133)mentioning

confidence: 99%

“…The samples were measured in triplicate and evaluated by using the comparative threshold cycle (∆∆C T ) method. 18S rRNA was used as the housekeeper reference due to its stable expression in dynamic FTC-133 cell cultures [18].…”

Section: Mrna Isolation and Quantitative Real-time Pcr (Ftc-133)mentioning

confidence: 99%

Fluid and Bubble Flow Detach Adherent Cancer Cells to Form Spheroids on a Random Positioning Machine

Cortés-Sánchez,

Melnik,

Sandt

et al. 2023

Cells

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In preparing space and microgravity experiments, the utilization of ground-based facilities is common for initial experiments and feasibility studies. One approach to simulating microgravity conditions on Earth is to employ a random positioning machine (RPM) as a rotary bioreactor. Combined with a suitable low-mass model system, such as cell cultures, these devices simulating microgravity have been shown to produce results similar to those obtained in a space experiment under real microgravity conditions. One of these effects observed under real and simulated microgravity is the formation of spheroids from 2D adherent cancer cell cultures. Since real microgravity cannot be generated in a laboratory on Earth, we aimed to determine which forces lead to the detachment of individual FTC-133 thyroid cancer cells and the formation of tumor spheroids during culture with exposure to random positioning modes. To this end, we subdivided the RPM motion into different static and dynamic orientations of cell culture flasks. We focused on the molecular activation of the mechanosignaling pathways previously associated with spheroid formation in microgravity. Our results suggest that RPM-induced spheroid formation is a two-step process. First, the cells need to be detached, induced by the cell culture flask’s rotation and the subsequent fluid flow, as well as the presence of air bubbles. Once the cells are detached and in suspension, random positioning prevents sedimentation, allowing 3D aggregates to form. In a comparative shear stress experiment using defined fluid flow paradigms, transcriptional responses were triggered comparable to exposure of FTC-133 cells to the RPM. In summary, the RPM serves as a simulator of microgravity by randomizing the impact of Earth’s gravity vector especially for suspension (i.e., detached) cells. Simultaneously, it simulates physiological shear forces on the adherent cell layer. The RPM thus offers a unique combination of environmental conditions for in vitro cancer research.

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Dexamethasone Selectively Inhibits Detachment of Metastatic Thyroid Cancer Cells during Random Positioning

Cited by 8 publications

References 91 publications

Current Knowledge about the Impact of Microgravity on Gene Regulation

Current Knowledge about the Impact of Microgravity on Gene Regulation

Tumor Models and Drug Targeting In Vitro—Where Are We Today? Where Do We Go from Here?

Fluid and Bubble Flow Detach Adherent Cancer Cells to Form Spheroids on a Random Positioning Machine

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