FABP5 is a key player in metabolic modulation and NF-κB dependent inflammation driving pleural mesothelioma

Our plain-English summary of FABP5 is a key player in metabolic modulation and NF-κB dependent inflammation driving pleural mesothelioma, by E. Vecchio, R. Gallo, S. Mimmi, et al (Communications Biology, 2025).

The study

• Authors: E. Vecchio, R. Gallo, S. Mimmi, D. Gentile, C. Giordano, E. Straface, R. Marino, C. Caiazza, A. Pastore, M.R. Ruocco, A. Arcucci, M. Schiavone, C. Palmieri, E. Iaccino, M. Stornaiuolo, I. Quinto, M. Mallardo, F. Martini, M. Tognon, G. Fiume
• Journal: Communications Biology
• Published: 2025;8(1):324
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) poses a significant challenge in oncology due to its intricate molecular and metabolic landscape, chronic inflammation, and heightened oxidative stress, which contribute to its notorious resilience and clinical complexities. Despite advancements, the precise mechanisms driving PM carcinogenesis remain elusive, impeding therapeutic progress. Here, we explore the interplay between tumor growth dynamics, lipid metabolism, and NF-κB dysregulation in malignant pleural mesothelioma, shedding light on novel molecular mechanisms underlying its pathogenesis. Our study reveals distinctive growth dynamics in PM cells, characterized by heightened proliferation, altered cell cycle progression, and resistance to apoptosis. Intriguingly, PM cells exhibit increased intracellular accumulation of myristic, palmitic, and stearic acids, suggestive of augmented lipid uptake and altered biosynthesis. Notably, we identify FABP5 as a key player in driving metabolic alterations and inflammation through NF-κB dysregulation in mesothelioma cells, distinguishing them from normal mesothelial cells. Silencing of FABP5 leads to significant alterations in cell dynamics, metabolism, and NF-κB activity, highlighting its potential as a therapeutic target. Our findings unveil a reciprocal relationship between lipid metabolism and inflammation in PM, providing a foundation for targeted therapeutic strategies. Overall, this comprehensive investigation offers insights into the intricate molecular mechanisms driving PM pathogenesis and identifies potential avenues for therapeutic intervention.

© 2025. The Author(s).

In plain English

This was a laboratory study of cells grown in dishes. It did not study people or asbestos exposure. The authors compared two pleural mesothelioma cell lines, IST-Mes2 and MPP89, with normal human primary mesothelial cells (HMC35). The mesothelioma cells contained more of several saturated fatty acids. For example, palmitic acid (16:0) measured 80.37 ± 7.22 in HMC35, 135.8 ± 6.3 in IST-Mes-2 and 116.85 ± 6.3 in MPP89 (pg/mg of protein). The mesothelioma cells also showed more reactive oxygen species and higher activity of NF-κB, a protein that switches on inflammation genes. Among the fatty acid transporters tested, FABP5 was specifically increased in the mesothelioma cells. When FABP5 was silenced, the mesothelioma cells grew more slowly, more of them died by apoptosis, and their NF-κB activity fell to levels seen in normal cells. The growth and apoptosis of the normal cells did not change. The authors concluded that FABP5 is a key player linking fat metabolism and NF-κB-driven inflammation in mesothelioma cells. They added that animal studies and clinical trials are needed.

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: In vitro laboratory study of cultured cell lines
• Who was studied: Two pleural mesothelioma cell lines (IST-Mes2 and MPP89) compared with normal human primary mesothelial cells (HMC35); no human subjects
• Exposure: No asbestos or fiber exposure was studied. The experimental treatments were TNF-α stimulation and silencing of the fatty acid transporter FABP5 with siRNA, compared against a scrambled control siRNA.
• Main results:
  • Myristic acid (14:0), pg/mg of protein: 3.83 ± 0.47 in normal HMC35 cells, 5.95 ± 0.45 in IST-Mes-2 and 5.56 ± 0.52 in MPP89 (p less than 0.05 for each mesothelioma line versus HMC35)
  • Palmitic acid (16:0), pg/mg of protein: 80.37 ± 7.22 in HMC35, 135.8 ± 6.3 in IST-Mes-2 and 116.85 ± 6.3 in MPP89 (p less than 0.05 for each mesothelioma line versus HMC35)
  • Stearic acid (18:0), pg/mg of protein: 71.26 ± 3.20 in HMC35, 137.24 ± 8.2 in IST-Mes-2 and 103.48 ± 6.2 in MPP89 (p less than 0.05 for each mesothelioma line versus HMC35)
  • Some fatty acids were lower in the mesothelioma lines. For example, PUFA 18:2 was 68.67 ± 5.31 in HMC35, 35.52 ± 4.27 in IST-Mes-2 and 50.04 ± 3.84 in MPP89 (p less than 0.05 for both)
  • The ADP/ATP ratio was lower in both mesothelioma lines than in the normal HMC35 cells
  • Mesothelioma cells produced more reactive oxygen species than normal mesothelial cells
  • In a reporter assay, NF-κB activity was higher in the mesothelioma lines than in HMC35, and TNF-alpha increased it further
  • CD36 was the main fatty acid transporter in both normal and mesothelioma cells, while FABP5 expression was increased specifically in the mesothelioma cell lines
  • In MPP89 compared with HMC35, expression of inflammatory genes was increased, including IL1A, IL1B, IL6, IL8 and CCL2
  • Silencing FABP5 reduced proliferation of IST-Mes2 and MPP89 cells but not of normal HMC35 cells
  • Silencing FABP5 increased apoptosis in both mesothelioma lines, while apoptosis in normal mesothelial cells was unaltered
  • Silencing FABP5 reduced lipid droplets and reduced NF-κB activity in mesothelioma cells to levels seen in normal mesothelial cells
  • Silencing FABP5 reduced DNA binding of the NF-κB subunit p65 only, and lowered expression of the inflammatory genes IL1B, IL6, CCL2 and IL8
• The authors' conclusion: The authors concluded that FABP5 is a key player driving metabolic changes and NF-κB-dependent inflammation in mesothelioma cells, distinguishing them from normal mesothelial cells. They described it as a potential therapeutic target.
• Limitations the authors state:
  • The authors acknowledged limits on clinical translation and on how widely the findings apply
  • The authors stated that animal studies and clinical trials are needed to test whether targeting FABP5 is effective and safe

Topics

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

Medical terms in this study, explained in our Lexicon: Inflammation, Pleural Mesothelioma, Chronic Inflammation, Oxidative Stress, Carcinogenesis, Apoptosis, Mesothelioma, Mesothelial Cells.

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