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

Our plain-English summary of Microgravity as a Tool to Investigate Cancer Induction in Pleura Mesothelial Cells, by V. Bonetto, C.A. Pagano, M. Sabbatini, et al (Current Issues in Molecular Biology, 2024).

The study

• Authors: V. Bonetto, C.A. Pagano, M. Sabbatini, V. Magnelli, M. Donadelli, E. Marengo, M.A. Masini
• Journal: Current Issues in Molecular Biology
• Published: 2024;46(10):10896-10912
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory study of cells grown in dishes. It did not test asbestos. Asbestos appears only in the background section as a known cause of mesothelioma. The authors grew MeT-5A cells, an immortalized line derived from pleural fluid of non-cancerous individuals, on a machine that keeps rotating the cells to simulate the low gravity of space, for 24 hours, 48 hours and 7 days. They compared these cells with cells kept under normal gravity and with BR95 cells, an epithelioid malignant pleural mesothelioma line. Some cells exposed to simulated microgravity detached and formed floating clumps, and the clumps became more numerous over time. Their internal scaffolding (microtubules and actin) became disorganized. Adhesion proteins and the tumor marker fibulin-3 changed, in some respects toward the pattern seen in the BR95 mesothelioma cells. Results came from three repeated experiments and are given mainly in figures. The authors concluded that simulated microgravity altered adhesion and scaffolding and led to markers associated with tumor transformation. They noted that the findings may apply only to these cell lines and need animal studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment; no human or animal subjects were studied
• Who was studied: MeT-5A cells, an immortalized non-cancerous mesothelial cell line derived from pleural fluid of non-cancerous individuals and purchased from ATCC. For comparison, BR95 epithelioid malignant pleural mesothelioma cells derived from pleural effusion of untreated patients. Work done at university departments in Alessandria and Verona, Italy. Data from three repeated experiments.
• Exposure: Simulated microgravity produced by continuous rotation on a Random Positioning Machine for 24 h, 48 h and 7 days, compared with ground control cells kept at normal gravity. No asbestos or other fiber exposure was studied.
• Main results:
  • Among MeT-5A cells under simulated microgravity, rounded detached cells formed floating clusters (called CLUMP cells) from 24 h onward, and the number of clusters increased with longer exposure
  • In both attached and CLUMP MeT-5A cells, the microtubule network became disarranged and fragmented, resembling BR95 mesothelioma cells. The total amount of alpha-tubulin did not change.
  • In attached MeT-5A cells, total vinculin (an adhesion protein) fell during 24 to 48 h of simulated microgravity and then rose after 7 days
  • In CLUMP cells, connexin-43 increased at 24 to 48 h and then decreased after 7 days, to a level similar to that in BR95 mesothelioma cells
  • The tumor marker fibulin-3 showed a mild signal in control and 24 h attached MeT-5A cells and a marked increase at 48 h and 7 days. It also rose strongly in CLUMP cells from 24 h, and was very high in BR95 cells.
  • NANOG protein, a stem-cell marker, was very low in control MeT-5A cells and increased within 24 h of simulated microgravity, remaining stable up to 7 days
  • p27, a tumor suppressor, increased in CLUMP cells after 24 h and then gradually declined at 48 h and 7 days. It was sparse in BR95 cells.
  • At the gene level in CLUMP cells, NANOG rose strongly at 24 h and then decreased at 48 h and 7 days compared with controls. CDH-1 decreased after 48 h.
• The authors' conclusion: The authors concluded that simulated microgravity caused alterations in adhesion and cytoskeletal stability factors in MeT-5A cells, with acquisition of stemness characteristics and markers associated with tumor transformation. They described the cells as diverging into an enhanced-adhesion path and a loss-of-adhesion, tumor-like path, and stated that several steps of the proposed mechanism remain speculative.
• Limitations the authors state:
  • Using only the MeT-5A and BR95 cell lines may restrict the findings to these cell types; a broader range of cell lines is needed
  • The cell types chosen focus the work on epithelioid-type mesothelioma
  • As an in vitro study, it would benefit from experiments in living animals
  • MeT-5A is an immortalized line and may not perfectly replicate primary mesothelial cells
  • The rotating machine may cause limited shear forces and centrifugal acceleration; the authors state these were evaluated previously and that flasks were placed near the platform center
  • Molecular pathways beyond the factors measured were not explored, and several proposed steps remain speculative

Topics

Medical terms in this study, explained in our Lexicon: Pleura, Mesothelial Cells, Mesothelioma, Fibulin-3, MeT-5A Cells.

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