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. 2024 Sep 27;46(10):10896-10912.
doi: 10.3390/cimb46100647.

Microgravity as a Tool to Investigate Cancer Induction in Pleura Mesothelial Cells

Valentina Bonetto  1 , Corinna Anais Pagano  1 , Maurizio Sabbatini  1 , Valeria Magnelli  1 , Massimo Donadelli  2 , Emilio Marengo  1 , Maria Angela Masini  1
Affiliations

Microgravity as a Tool to Investigate Cancer Induction in Pleura Mesothelial Cells

Valentina Bonetto et al. Curr Issues Mol Biol. .

Abstract

The present work shows that the exposure of mesothelial cells to simulated microgravity changes their cytoskeleton and adhesion proteins, leading to a cell switch from normal towards tumoral cells. Immunohistochemical and molecular data were obtained from both MeT-5A exposed to simulated microgravity and BR95 mesothelioma cell lines. Simulated microgravity was found to affect the expression of actin, vinculin, and connexin-43, altering their quantitative and spatial distribution pattern inside the cell. The analysis of the tumoral markers p27, CD44, Fibulin-3, and NANOG and the expression of genes related to cancer transformation such as NANOG, CDH-1, and Zeb-1 showed that the simulated microgravity environment led to expression patterns in MeT-5A cells similar to those observed in BR95 cells. The alteration in both quantitative expression and structural organization of the cytoskeleton and adhesion/communication proteins can thus be considered a pivotal mechanism involved in the cellular shift towards tumoral progression.

Keywords: BR95 cells; Fibulin-3; MeT-5A cells; NANOG; connexin-43; focal contacts; mesothelioma.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Microphotograph panel illustrating the immunofluorescence localization of α-Tubulin in MeT5A cells (A,B) in their agglomerate (CLUMP) disposition (C) and BR95 cells (D), following normogravity (A) or microgravity at 48 h (B,C). The quantitative expression of several proteins analyzed is shown in the bar-graph and western blot panel. Calibration bar = 20 µm. No statistical difference detected. N = 3.
Figure 2
Figure 2
Microphotograph panel illustrating the immunofluorescence localization of Actin (A–C), Vinculin (D–F), and connexin-43 (G–I) in adherent MeT5A cells, following normogravity (A,D,G) or microgravity at 48 h (B,E,H) and 7 days (C,F,I). In (D–F), the frame shows the observed focal contacts in high detail. The quantitative expression of several proteins is shown in the bar-graph and western blot panel. Calibration bar = 20 µm. a = p < 0.05 vs. ctr; b = p < 0.05 vs. 24 h; * = p < 0.05 vs. other experimental groups. N = 3.
Figure 3
Figure 3
Microphotograph panel illustrating the immunofluorescence localization of Actin (A–C), Vinculin (D–F), and connexin-43 (G–I) in adherent MeT5A cells (A,D,G) in their agglomerate (CLUMP) disposition (B,E,H) and adherent BR95 cells (C,F,I), following normogravity (A,D,G) or microgravity at 7 days (B,E,H). The quantitative expression of several proteins analyzed is shown in the bar-graph and western blot panel. Calibration bar = 20 µm. a = p < 0.05 vs. ctr; b = p < 0.05 vs. 24 h; * = p < 0.05 vs. other experimental groups. N = 3.
Figure 4
Figure 4
Panel illustrating the expression of several proteins analyzed in adherent MeT5A cells. The quantitative expression of several proteins analyzed is shown in the bar-graph. a = p < 0.05 vs. ctr; b = p < 0.05 vs. 24 h; * = p < 0.05 vs. other experimental groups. N = 3.
Figure 5
Figure 5
Panel illustrating the expression of several proteins analyzed in MeT5A cells in their (CLUMP) disposition. The quantitative expression of several proteins analyzed is shown in the bar-graph. a = p < 0.05 vs. ctr; b = p < 0.05 vs. 24 h; c = p < 0.05 vs. 48 h; * = p < 0.05 vs. other experimental groups. N = 3.
Figure 6
Figure 6
Bar-graph illustrating the expression of several gene analyzed in MeT5A cells in their (CLUMP) disposition, following normogravity or microgravity application and in adherent BR95 cells. a = p < 0.05 vs. ctr; b = p < 0.05 vs. 24 h; c = p < 0.05 vs. 48 h; * = p < 0.05 vs. other experimental groups. N = 3.
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