Microgravity Affects Thyroid Cancer Cells during the TEXUS-53 Mission Stronger than Hypergravity

Kopp, Sascha; Krüger, Marcus; Bauer, Johann; Wehland, Markus; Corydon, Thomas J.; Sahana, Jayashree; Nassef, Mohamed Zakaria; Melnik, Daniela; Bauer, Thomas Johann; Schulz, Herbert; Schütte, Andreas; Schmitz, Burkhard; Oltmann, Hergen; Feldmann, Stefan; Infanger, Manfred; Grimm, Daniela

doi:10.3390/ijms19124001

Cited by 20 publications

(26 citation statements)

References 75 publications

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“…It is plausible that this change occurs because the cells are trying to resist the s-µg conditions and hold onto the ECM, although this does not match the generally unchanged amounts of TLN1 gene expression in our experiment. In contrast to the results of this study, FTC-133 cells exposed to µg showed no change in VCL expression and decreased TLN mRNA [75]. Thus, PC-3 cells and FTC-133 cells show a different regulation of FA gene expression and, possibly, synthesis or secretion of proteins.…”

Section: Changes In the Cytoskeleton And The Extracellular Matrixcontrasting

confidence: 99%

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

Hybel

Dietrichs

Sahana

et al. 2020

IJMS

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Prostate cancer is one of the leading causes of cancer mortality in men worldwide. An unusual but unique environment for studying tumor cell processes is provided by microgravity, either in space or simulated by ground-based devices like a random positioning machine (RPM). In this study, prostate adenocarcinoma-derived PC-3 cells were cultivated on an RPM for time periods of 3 and 5 days. We investigated the genes associated with the cytoskeleton, focal adhesions, extracellular matrix, growth, survival, angiogenesis, and metastasis. The gene expression of signaling factors of the vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), and PI3K/AKT/mTOR (PAM) pathways was investigated using qPCR. We performed immunofluorescence to study the cytoskeleton, histological staining to examine the morphology, and a time-resolved immunofluorometric assay to analyze the cell culture supernatants. When PC-3 cells were exposed to simulated microgravity (s-µg), some cells remained growing as adherent cells (AD), while most cells detached from the cell culture flask bottom and formed multicellular spheroids (MCS). After 3-day RPM exposure, PC-3 cells revealed significant downregulation of the VEGF, SRC1, AKT, MTOR, and COL1A1 gene expression in MCS, whereas FLT1, RAF1, MEK1, ERK1, FAK1, RICTOR, ACTB, TUBB, and TLN1 mRNAs were not significantly changed. ERK2 and TLN1 were elevated in AD, and FLK1, LAMA3, COL4A5, FN1, VCL, CDH1, and NGAL mRNAs were significantly upregulated in AD and MCS after 3 days. After a 5-day culture in s-µg, the PC-3 cells showed significant downregulations of VEGF mRNA in AD and MCS, and FN1, CDH1, and LAMA3 in AD and SCR1 in MCS. In addition, we measured significant upregulations in FLT1, AKT, ERK1, ERK2, LCN2, COL1A1, TUBB, and VCL mRNAs in AD and MCS, and increases in FLK1, FN1, and COL4A5 in MCS as well as LAMB2, CDH1, RAF1, MEK1, SRC1, and MTOR mRNAs in AD. FAK1 and RICTOR were not altered by s-µg. In parallel, the secretion rate of VEGFA and NGAL proteins decreased. Cytoskeletal alterations (F-actin) were visible, as well as a deposition of collagen in the MCS. In conclusion, RPM-exposure of PC-3 cells induced changes in their morphology, cytoskeleton, and extracellular matrix protein synthesis, as well as in their focal adhesion complex and growth behavior. The significant upregulation of genes belonging to the PAM pathway indicated their involvement in the cellular changes occurring in microgravity.

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Section: Changes In the Cytoskeleton And The Extracellular Matrixcontrasting

confidence: 99%

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

Hybel

Dietrichs

Sahana

et al. 2020

IJMS

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“…In particular, a microgravity environment can change the migration and invasion ability of tumor cells . According to reports in the literature, related studies have involved thyroid cancer, breast cancer, gastric cancer, lung cancer, colorectal cancer, leukemia, malignant glioma, liver cancer, and neuroblastoma …”

Section: Discussionmentioning

confidence: 99%

“…Some studies have used multiple time points to simulate the effects of microgravity on cells, whereas others have used a single time point (e.g. 6 min, 1 day, 2 days, 3 days, and 14 days), but all of these studies have found that simulated microgravity has a wide range of effects on a variety of cells. A single time point of 7 days was used in the present study, and there is a contingency in the design of an experiment with a single time point.…”

Section: Discussionmentioning

confidence: 99%

Effects of rotary cell culture system‐simulated microgravity on the ultrastructure and biological behavior of human MDA‐MB‐231 breast cancer cells

Jiang

Chen

et al. 2019

Precision Radiation Oncology

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Objective: This study aimed to investigate changes in the ultrastructure, apoptosis, cycle progression, and migration ability of human MDA-MB-231 breast cancer cells under simulated microgravity conditions. Methods: MDA-MB-231 breast cancer cells were cultured in a rotary cell culture system bioreactor to simulate microgravity for 7 days. The cells were randomly divided into a simulated microgravity (SMG) group and normal gravity control (NG) group. Changes in apoptosis, ultrastructure, cell cycle, and migration ability were evaluated.Results: Transmission electron microscopy showed that cells in the SMG group had more secondary lysosomes than the NG groups. The flow cytometry assay showed that the proportion of apoptotic cells in the SMG group was significantly increased compared with the NG group; additionally, the median and interquartile spacing of the proportion of cells in the G0/G1 phase in the SMG group was lower than in the NG group, but the proportion of cells in the S phase was increased in the SMG group compared with the NG group. The transwell migration assay showed that cell migration in the SMG group was significantly reduced compared with the NG group. The expression of BCL-2 and MMP9 in the SMG group was decreased compared with the NG group, whereas the expression of cyclin D3 in the SMG group was increased. Conclusion: Simulated microgravity through rotary cell culture system had significant effects on human MDA-MB-231 breast cancer cells: the cell cycle and ultrastructure were impaired, apoptosis increased, migration ability decreased, and the expression of BCL-2, cyclin D3, and MMP9 were affected. K E Y W O R D S cell apoptosis, cell migration, cell ultrastructure, MDA-MB-231 breast cancer, simulated microgravity 1

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“…The omics technology revealed changes of expression and/or accumulation of adhesion proteins under microgravity in AD and MCS cells as compared to control cells cultured under 1g-conditions [5,6]. Hence, additional information was collected about microgravity-dependent posttranslational modifications [20], including phosphorylation [9,21], ubiquitination [22,23], or isgylation [6,24], and about the intracellular translocation of adhesion proteins [25,26].…”

Section: Introductionmentioning

confidence: 99%

Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion—An Omics Network Approach

Bauer

Gombocz²,

Wehland

et al. 2020

IJMS

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The adhesion behavior of human tissue cells changes in vitro, when gravity forces affecting these cells are modified. To understand the mechanisms underlying these changes, proteins involved in cell-cell or cell-extracellular matrix adhesion, their expression, accumulation, localization, and posttranslational modification (PTM) regarding changes during exposure to microgravity were investigated. As the sialylation of adhesion proteins is influencing cell adhesion on Earth in vitro and in vivo, we analyzed the sialylation of cell adhesion molecules detected by omics studies on cells, which change their adhesion behavior when exposed to microgravity. Using a knowledge graph created from experimental omics data and semantic searches across several reference databases, we studied the sialylation of adhesion proteins glycosylated at their extracellular domains with regards to its sensitivity to microgravity. This way, experimental omics data networked with the current knowledge about the binding of sialic acids to cell adhesion proteins, its regulation, and interactions in between those proteins provided insights into the mechanisms behind our experimental findings, suggesting that balancing the sialylation against the de-sialylation of the terminal ends of the adhesion proteins’ glycans influences their binding activity. This sheds light on the transition from two- to three-dimensional growth observed in microgravity, mirroring cell migration and cancer metastasis in vivo.

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Microgravity Affects Thyroid Cancer Cells during the TEXUS-53 Mission Stronger than Hypergravity

Cited by 20 publications

References 75 publications

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

Effects of rotary cell culture system‐simulated microgravity on the ultrastructure and biological behavior of human MDA‐MB‐231 breast cancer cells

Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion—An Omics Network Approach

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