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Special Issue "Microgravity and Cell Adherence"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 December 2019.

Special Issue Editor

Dr. Johann Bauer
E-Mail
Guest Editor
Max Planck Institute, Martinsried, Germany
Interests: cell adhesion; organoid formation

Special Issue Information

Dear colleagues,

Cell adherence is changed when cells are exposed to microgravity. This is true for human and animal tissue cells, as well as for microorganisms exposed to simulated or real microgravity. In human or animal cells, changes of adherence became especially apparent when scaffold-free organoid formation was investigated, which included the cells’ detachment from the surface of the culture flasks, followed by three-dimensional aggregation. In this process, distinct proteins and genes coding for them have already been identified, which contribute either to a cell’s adherence to a substratum or to contact with neighboring cells. Furthermore, adhesion-dependent initiation of microbial biofilm formation can be triggered by microgravity-induced changes of gene expression patterns, protein accumulation, and carbohydrate metabolism.

In both cases, the kind and force of adherence are regulated by external and internal signals. External signals are exerted by features of the surface to which the cells adhere. Internal signals have been described repeatedly. However, their generation by the influence of microgravity requires further investigation.

Articles and reviews will be collected in which either the chemical/biochemical background of external signals is described, or cellular mechanisms are unveiled that up- or down-regulate the cells’ adhesion to their environment under microgravity.

Dr. Johann Bauer
Guest Editor

Manuscript Submission Information

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Keywords

  • Cell monolayer
  • Organoid formation
  • Adhesion proteins
  • Tight junction

Published Papers (4 papers)

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Research

Open AccessArticle
The Role of C-X-C Chemokine Receptor Type 4 (CXCR4) in Cell Adherence and Spheroid Formation of Human Ewing’s Sarcoma Cells under Simulated Microgravity
Int. J. Mol. Sci. 2019, 20(23), 6073; https://doi.org/10.3390/ijms20236073 - 02 Dec 2019
Abstract
We studied the behavior of Ewing’s Sarcoma cells of the line A673 under simulated microgravity (s-µg). These cells express two prominent markers—the oncogene EWS/FLI1 and the chemokine receptor CXCR4, which is used as a target of treatment in several types of cancer. The [...] Read more.
We studied the behavior of Ewing’s Sarcoma cells of the line A673 under simulated microgravity (s-µg). These cells express two prominent markers—the oncogene EWS/FLI1 and the chemokine receptor CXCR4, which is used as a target of treatment in several types of cancer. The cells were exposed to s-µg in a random-positioning machine (RPM) for 24 h in the absence and presence of the CXCR4 inhibitor AMD3100. Then, their morphology and cytoskeleton were examined. The expression of selected mutually interacting genes was measured by qRT-PCR and protein accumulation was determined by western blotting. After 24 h incubation on the RPM, a splitting of the A673 cell population in adherent and spheroid cells was observed. Compared to 1 g control cells, EWS/FLI1 was significantly upregulated in the adherent cells and in the spheroids, while CXCR4 and CD44 expression were significantly enhanced in spheroids only. Transcription of CAV-1 was upregulated and DKK2 and VEGF-A were down-regulated in both, adherent in spheroid cells, respectively. Regarding, protein accumulation EWS/FLI1 was enhanced in adherent cells only, but CD44 decreased in spheroids and adherent cells. Inhibition of CXCR4 did not change spheroid count, or structure. Under s-µg, the tumor marker EWS/FLI1 is intensified, while targeting CXCR4, which influences adhesion proteins, did not affect spheroid formation. Full article
(This article belongs to the Special Issue Microgravity and Cell Adherence)
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Open AccessArticle
Short-Term Microgravity Influences Cell Adhesion in Human Breast Cancer Cells
Int. J. Mol. Sci. 2019, 20(22), 5730; https://doi.org/10.3390/ijms20225730 - 15 Nov 2019
Abstract
With the commercialization of spaceflight and the exploration of space, it is important to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We examined the influence of r-µg, simulated microgravity (s-µg, incubator [...] Read more.
With the commercialization of spaceflight and the exploration of space, it is important to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We examined the influence of r-µg, simulated microgravity (s-µg, incubator random positioning machine (iRPM)), hypergravity (hyper-g), and vibration (VIB) on triple-negative breast cancer (TNBC) cells (MDA-MB-231 cell line) with the aim to study early changes in the gene expression of factors associated with cell adhesion, apoptosis, nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. We had the opportunity to attend a parabolic flight (PF) mission and to study changes in RNA transcription in the MDA-MB cells exposed to PF maneuvers (29th Deutsches Zentrum für Luft- und Raumfahrt (DLR) PF campaign). PF maneuvers induced an early up-regulation of ICAM1, CD44 and ERK1 mRNAs after the first parabola (P1) and a delayed upregulation of NFKB1, NFKBIA, NFKBIB, and FAK1 after the last parabola (P31). ICAM-1, VCAM-1 and CD44 protein levels were elevated, whereas the NF-κB subunit p-65 and annexin-A2 protein levels were reduced after the 31st parabola (P31). The PRKCA, RAF1, BAX mRNA were not changed and cleaved caspase-3 was not detectable in MDA-MB-231 cells exposed to PF maneuvers. Hyper-g-exposure of the cells elevated the expression of CD44 and NFKBIA mRNAs, iRPM-exposure downregulated ANXA2 and BAX, whereas VIB did not affect the TNBC cells. The early changes in ICAM-1 and VCAM-1 and the rapid decrease in the NF-κB subunit p-65 might be considered as fast-reacting, gravity-regulated and cell-protective mechanisms of TNBC cells exposed to altered gravity conditions. This data suggest a key role for the detected gravity-signaling elements in three-dimensional growth and metastasis. Full article
(This article belongs to the Special Issue Microgravity and Cell Adherence)
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Open AccessArticle
Apoptosis Induction and Alteration of Cell Adherence in Human Lung Cancer Cells under Simulated Microgravity
Int. J. Mol. Sci. 2019, 20(14), 3601; https://doi.org/10.3390/ijms20143601 - 23 Jul 2019
Cited by 1
Abstract
Background: Lung cancer cells are known to change proliferation and migration under simulated microgravity. In this study, we sought to evaluate cell adherence, apoptosis, cytoskeleton arrangement, and gene expression under simulated microgravity. Methods: Human lung cancer cells were exposed to simulated microgravity in [...] Read more.
Background: Lung cancer cells are known to change proliferation and migration under simulated microgravity. In this study, we sought to evaluate cell adherence, apoptosis, cytoskeleton arrangement, and gene expression under simulated microgravity. Methods: Human lung cancer cells were exposed to simulated microgravity in a random-positioning machine (RPM). Cell morphology and adherence were observed under phase-contrast microscopy, cytoskeleton staining was performed, apoptosis rate was determined, and changes in gene and protein expression were detected by real-time PCR with western blot confirmation. Results: Three-dimensional (3D)-spheroid formation was observed under simulated microgravity. Cell viability was not impaired. Actin filaments showed a shift in alignment from longitudinal to spherical. Apoptosis rate was significantly increased in the spheroids compared to the control. TP53, CDKN2A, PTEN, and RB1 gene expression was significantly upregulated in the adherent cells under simulated microgravity with an increase in corresponding protein production for p14 and RB1. SOX2 expression was significantly upregulated in the adherent cells, but protein was not. Gene expressions of AKT3, PIK3CA, and NFE2L2 remained unaltered. Conclusion: Simulated microgravity induces alteration in cell adherence, increases apoptosis rate, and leads to upregulation of tumor suppressor genes in human lung cancer cells. Full article
(This article belongs to the Special Issue Microgravity and Cell Adherence)
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Open AccessArticle
Real Microgravity Influences the Cytoskeleton and Focal Adhesions in Human Breast Cancer Cells
Int. J. Mol. Sci. 2019, 20(13), 3156; https://doi.org/10.3390/ijms20133156 - 28 Jun 2019
Cited by 5
Abstract
With the increasing number of spaceflights, it is crucial to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We tested the effect of r-µg on MCF-7 breast cancer cells with the objective to investigate cytoskeletal [...] Read more.
With the increasing number of spaceflights, it is crucial to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We tested the effect of r-µg on MCF-7 breast cancer cells with the objective to investigate cytoskeletal alterations and early changes in the gene expression of factors belonging to the cytoskeleton, extracellular matrix, focal adhesion, and cytokines. In the Technische Experimente unter Schwerelosigkeit (TEXUS) 54 rocket mission, we had the opportunity to conduct our experiment during 6 min of r-µg and focused on cytoskeletal alterations of MCF-7 breast cancer cells expressing the Lifeact-GFP marker protein for the visualization of F-actin as well as the mCherry-tubulin fusion protein using the Fluorescence Microscopy Analysis System (FLUMIAS) for fast live-cell imaging under r-µg. Moreover, in a second mission we investigated changes in RNA transcription and morphology in breast cancer cells exposed to parabolic flight (PF) maneuvers (31st Deutsches Zentrum für Luft- und Raumfahrt (DLR) PF campaign). The MCF-7 cells showed a rearrangement of the F-actin and tubulin with holes, accumulations in the tubulin network, and the appearance of filopodia- and lamellipodia-like structures in the F-actin cytoskeleton shortly after the beginning of the r-µg period. PF maneuvers induced an early up-regulation of KRT8, RDX, TIMP1, CXCL8 mRNAs, and a down-regulation of VCL after the first parabola. E-cadherin protein was significantly reduced and is involved in cell adhesion processes, and plays a significant role in tumorigenesis. Changes in the E-cadherin protein synthesis can lead to tumor progression. Pathway analyses indicate that VCL protein has an activating effect on CDH1. In conclusion, live-cell imaging visualized similar changes as those occurring in thyroid cancer cells in r-µg. This result indicates the presence of a common mechanism of gravity perception and sensation. Full article
(This article belongs to the Special Issue Microgravity and Cell Adherence)
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