Extracellular stressors change BBSome expression of benign mesothelial and primary pleural mesothelioma cells and affect cell adhesion and migration

Our plain-English summary of Extracellular stressors change BBSome expression of benign mesothelial and primary pleural mesothelioma cells and affect cell adhesion and migration, by R.M. Jagirdar, E. Rouka, E. Pitaraki, et al (Physiological Reports, 2026).

The study

• Authors: R.M. Jagirdar, E. Rouka, E. Pitaraki, S.I. Sinis, C. Varsamas, E.D. Papazoglou, L. Giannakou, P.I. Tzamalas, O.S. Kotsiou, A. Giannou, C. Hatzoglou, N.M. Rahman, K.I. Gourgoulianis, S.G. Zarogiannis
• Journal: Physiological Reports
• Published: 2026;14(12):e70983
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelial cells have a primary cilium (PC), a solitary sensory organelle facing the extracellular environment. The BBSome is critical for the PC function and comprises several BBS proteins. Extracellular stimuli, like the ones encountered during a pleural effusion (osmotic, inflammatory, and oxidative stress-related signals) could influence the PC and BBSome. Using 2D and 3D culture models of benign mesothelial and primary malignant pleural mesothelioma cells we explored the BBSome components gene expression under hyperosmotic, inflammatory, and oxidative stress. We also assessed their effects in combination with PC perturbing drugs in the context of cell adhesion and cell migration, which are critical for tissue healing. These extracellular stimuli changed the expression patterns of BBS genes, while changes in cell adhesion were dependent on the cell and stimulus type. Cell migration was also sensitive to stress stimuli and the native PC length was critical in this context. Our results provide considerable insight into the molecular and phenotypical changes underlying PC responses of benign and malignant mesothelial cells to extracellular stimuli. Further research will be needed to assess the potential therapeutic implications of PC extracellular stimulation in malignant pleural disease.

© 2026 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

In plain English

This laboratory short report did not study asbestos or asbestos-exposed people. The authors grew a benign human mesothelial cell line (MeT-5A) and malignant pleural mesothelioma cells from the pleural effusion of one male patient with epithelioid mesothelioma. They exposed the cells to three stresses relevant to pleural fluid: high protein (bovine serum albumin) to raise osmotic pressure, bacterial lipopolysaccharide (LPS) as an inflammatory signal, and hydrogen peroxide as oxidative stress. They measured expression of BBSome genes (their RNA levels). These genes are linked to the primary cilium, a sensory structure on cells. They also tested cell attachment and movement, sometimes adding drugs that remove or lengthen the cilium. The stresses changed BBSome gene expression in ways that depended on cell type and on whether cells grew flat or as three-dimensional clusters. Effects were smaller in clusters. Hydrogen peroxide reduced attachment of both cell types. High protein and LPS increased attachment of the mesothelioma cells. In both cell types, adding either cilium drug alongside a stress lowered movement compared with that stress alone. The authors noted they did not directly examine the cilia, and that lithium chloride affects other cell pathways.

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, published as a short report; cells grown flat (2D) and as 3D spheroids
• Who was studied: The human benign immortalized mesothelial cell line MeT-5A (male donor) and primary epithelioid malignant pleural mesothelioma (pMPM) cells isolated from the pleural effusion of one male patient; ethics approval from the University Hospital of Larissa, Greece
• Exposure: No asbestos or fiber exposure was studied. Cells were exposed to hyperosmotic stress (7.2% bovine serum albumin), an inflammatory stimulus (LPS 5 μg/mL) and oxidative stress (100 μM H2O2). Some experiments added 30 mM ammonium sulfate (to remove the primary cilium) or 50 mM lithium chloride (to lengthen it).
• Main results:
  • In flat (2D) cultures of the benign MeT-5A cells, H2O2 increased expression of the tested BBS genes except BBS18. High BSA increased expression of BBS1, BBS7 and BBS18. LPS caused no changes.
  • In 2D cultures of the mesothelioma (pMPM) cells, the stimuli reduced BBS gene expression.
  • In 3D spheroid cultures of both cell types, the stimuli had much smaller effects on BBSome gene expression.
  • In MeT-5A cells, H2O2 lowered cell adhesion to 44.28% (plus or minus 8.31%), compared with 102.1% in controls (p less than 0.001).
  • In pMPM cells, cell adhesion rose with BSA (400.7%) and with LPS (431.2%), compared with 102.5% in controls (n = 18). It fell with H2O2 (20.16%).
  • High BSA lowered the cell migration index in both cell types: in MeT-5A cells from 0.71 (control) to 0.42, and in pMPM cells from 0.72 (control) to 0.53. In pMPM cells, H2O2 also lowered it, to 0.37.
  • When either cilium-altering drug was added alongside BSA, LPS or H2O2, migration fell compared with that stimulus alone, in both cell types. For example, in pMPM cells with BSA the migration index was 0.49; it fell to 0.08 with ammonium sulfate and to 0.27 with lithium chloride (p less than 0.001). The drugs were not reported tested without a stimulus.
• The authors' conclusion: The authors concluded that stimuli relevant to pleural effusions change BBSome gene expression and alter mesothelial cell adhesion and migration. They added that these effects depend on cell type and on whether cells are grown in 2D or 3D.
• Limitations the authors state:
  • The primary cilium itself (its shape, frequency and protein expression) was not directly examined. Gene transcript levels may not reflect changes in cilium structure or function.
  • Lithium affects many signaling pathways apart from the cilium, so some effects may not be cilium-related.
  • No dose–response testing was done, so some effects may reflect nonspecific stress or toxicity at the concentrations used.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelial Cells, Pleural Effusion, Oxidative Stress.

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