Microgravity-based Modulation of VEGF Expression in Human Thyroid Carcinoma Cells

Melnik, Daniela; Krüger, Marcus; Kopp, Sascha; Wehland, Markus; Bauer, Johann; Infanger, Manfred; Grimm, Daniela

doi:10.3389/conf.fphys.2018.26.00002

Cited by 6 publications

(8 citation statements)

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“…As VEGF-A was found increased and VEGF-D serum levels were reported to be reduced in patients suffering from high-stage thyroid cancer [93,94], the authors concluded that µ g possibly triggers some antitumor pathways involving IL-15 [48]. Consistent with these results a down-regulation of VEGFA was also found in the space-flown cells after the CellBox-2 mission, whereas the mRNA level of VEGFA stayed rather constant during a respective RPM experiment [54]. This VEGF discrepancy was often observed when results of simulated µ g experiments were compared with data from real µ g studies.…”

Section: Research On Thyroid Cancer Cells In Microgravitymentioning

confidence: 72%

“…The CellBox-2 mission in 2017 allowed to investigate the effects of real µ g on the transcriptome and proteome of FTC-133 cells. The cells formed MCS in space and interestingly, these spheroids differed from MCS generated on an RPM by an enhanced release of VEGF [54]. As VEGF has a key role in neoangiogenesis, the enhanced production suggests a different angiogenic potential of thyroid cancer cells in space.…”

Section: Research On Thyroid Cancer Cells In Microgravitymentioning

confidence: 99%

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Fighting Thyroid Cancer with Microgravity Research

Krüger

Melnik

Kopp

et al. 2019

IJMS

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Microgravity in space or simulated by special ground-based devices provides an unusual but unique environment to study and influence tumour cell processes. By investigating thyroid cancer cells in microgravity for nearly 20 years, researchers got insights into tumour biology that had not been possible under normal laboratory conditions: adherently growing cancer cells detach from their surface and form three-dimensional structures. The cells included in these multicellular spheroids (MCS) were not only altered but behave also differently to those grown in flat sheets in normal gravity, more closely mimicking the conditions in the human body. Therefore, MCS became an invaluable model for studying metastasis and developing new cancer treatment strategies via drug targeting. Microgravity intervenes deeply in processes such as apoptosis and in structural changes involving the cytoskeleton and the extracellular matrix, which influence cell growth. Most interestingly, follicular thyroid cancer cells grown under microgravity conditions were shifted towards a less-malignant phenotype. Results from microgravity research can be used to rethink conventional cancer research and may help to pinpoint the cellular changes that cause cancer. This in turn could lead to novel therapies that will enhance the quality of life for patients or potentially develop new preventive countermeasures.

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Section: Research On Thyroid Cancer Cells In Microgravitymentioning

confidence: 72%

Section: Research On Thyroid Cancer Cells In Microgravitymentioning

confidence: 99%

Fighting Thyroid Cancer with Microgravity Research

Krüger

Melnik

Kopp

et al. 2019

IJMS

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“…Moreover, studies on cells exposed to r-µg for a short time, as performed by means of TEXUS (TX) sounding rocket missions (6 min) and parabolic flights (22 s), have demonstrated changes in the structure and organisation of the cytoskeleton as well as alterations in gene expression patterns [18,19]. Using a suitable hardware, TCC have been investigated in space during three different spaceflights, each lasting about 10 days [20][21][22]. After the SimBox/Shenzhou-8 spaceflight, there were spheroids of considerable size that could be observed as well as important and significant shifts in the gene expression pattern [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…To determine the impact of r-µg (spaceflight) on TCC, the CellBox-2 mission was performed [20]. In this mission to the International Space Station (ISS) flown in December 2017, a lower temperature (28 • C) during the pre-launch phase avoided the formation of a confluent cell monolayer, despite some delay in the launch.…”

Section: Introductionmentioning

confidence: 99%

The CellBox-2 Mission to the International Space Station: Thyroid Cancer Cells in Space

Melnik

Krüger

Schulz

et al. 2021

IJMS

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A spaceflight to the International Space Station (ISS) is a dream of many researchers. We had the chance to investigate the effect of real microgravity (CellBox-2 Space mission) on the transcriptome and proteome of FTC-133 human follicular thyroid cancer cells (TCC). The cells had been sent to the ISS by a Falcon 9 rocket of SpaceX CRS-13 from Cape Canaveral (United States) and cultured in six automated hardware units on the ISS before they were fixed and returned to Earth. Multicellular spheroids (MCS) were detectable in all spaceflight hardware units. The VCL, PXN, ITGB1, RELA, ERK1 and ERK2 mRNA levels were significantly downregulated after 5 days in space in adherently growing cells (AD) and MCS compared with ground controls (1g), whereas the MIK67 and SRC mRNA levels were both suppressed in MCS. By contrast, the ICAM1, COL1A1 and IL6 mRNA levels were significantly upregulated in AD cells compared with 1g and MCS. The protein secretion measured by multianalyte profiling technology and enzyme-linked immunosorbent assay (AngiogenesisMAP®, extracellular matrix proteins) was not significantly altered, with the exception of elevated angiopoietin 2. TCC in space formed MCS, and the response to microgravity was mainly anti-proliferative. We identified ERK/RELA as a major microgravity regulatory pathway.

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“…106 In paracrine studies, cell-conditioned medium extracted from s-μg culture was reported to have a cross-pathogenic effect on endothelial cell and smooth muscle cell proliferation and migration compared to normal gravity-conditioned medium. 107 Real microgravity was found to enhance vascular endothelial growth factor (VEGF) expression in thyroid carcinoma spheroid F I G U R E 4 Comparison of how different culture medium volumes and flow in s-μg experiments can affect autocrine signaling cultures, 108 but both VEGF secretion and VEGF expression decreased in s-μg (RPM) culture, where differences may be attributed to hypoxia. [109][110][111][112] Reduced autocrine signaling due to full vessel dilution may be an underlying factor whether for as-is culture or conditioned medium in paracrine s-μg studies.…”

Section: The Effect Of Culture Medium Volume On Autocrine and Paracrinementioning

confidence: 99%

Factors implicating the validity and interpretation of mechanobiology studies in simulated microgravity environments

Poon

2020

Engineering Reports

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Simulated microgravity (s-μg) devices provide unique conditions for elucidating the effects of gravitational unloading on biological processes and are increasingly being applied for mechanobiology studies. However, without proper characterization of the mechanical environment generated by these systems, the interpretation of results is confounded and limited. Furthermore, the cell culture approaches central to s-μg experimentation introduces new factors that can fundamentally affect results, but these are currently not addressed. It is essential to understand the complete culture environment and how constituent conditions can individually and synergistically affect cellular responses in order to correctly interpret results, otherwise outcomes may be misattributed to the effects of microgravity alone. For the benefit of the growing space biology community, this article critically reviews a typical s-μg cell culture environment in terms of three key conditions: fluid-mediated mechanical stimuli, oxygen tension and biochemical. These and the implications of other experimental variables for biological analysis are categorically discussed. A new set of controls is proposed to properly evaluate the respective effects of these conditions in s-μg culture, along with a reporting matrix and potential strategies for addressing the current limitations of simulated microgravity devices as a platform for mechanobiology research.

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Microgravity-based Modulation of VEGF Expression in Human Thyroid Carcinoma Cells

Cited by 6 publications

References 0 publications

Fighting Thyroid Cancer with Microgravity Research

Fighting Thyroid Cancer with Microgravity Research

The CellBox-2 Mission to the International Space Station: Thyroid Cancer Cells in Space

Factors implicating the validity and interpretation of mechanobiology studies in simulated microgravity environments

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