Malignant pleural fluid from mesothelioma has potent biological activities

Our plain-English summary of Malignant pleural fluid from mesothelioma has potent biological activities, by H.M. Cheah, S.M. Lansley, J.F. Varano Della Vergiliana, et al (Respirology, 2017).

The study

• Authors: H.M. Cheah, S.M. Lansley, J.F. Varano Della Vergiliana, A.L. Tan, R. Thomas, S.L. Leong, J. Creaney, Y.C. Lee
• Journal: Respirology
• Published: 2017;22(1):192-199
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background And Objective: Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth mediators but its contribution to tumour biology has not been investigated. We aimed to examine the potential effects of MPE in promoting growth, migration and chemo-resistance of mesothelioma.

Methods: Pleural fluid samples from 151 patients (56 mesothelioma, 60 metastatic pleural cancer and 35 benign) were used. Seven validated human mesothelioma cell lines and three primary cultured mesothelioma lines were employed.

Results: Pleural fluid from mesothelioma patients (diluted to 30%) consistently stimulated cell proliferation (trypan-blue cell viability assay) in five mesothelioma cell lines tested by (median) 2.23-fold over controls (all P < 0.0001). The fluid also induced cell migration by (median) 2.13-fold in six mesothelioma cell lines using scratch-wound assay. In a murine flank model of mesothelioma, tumour infused with daily instillations of pleural fluid grew significantly faster over saline controls (median 52.5 cm2 vs 28.0 cm2 at day 13, P = 0.028). Addition of MPE (diluted to 30%) to culture media significantly protected mesothelioma from cisplatin/pemetrexed-induced cell death in all three cell lines tested (median fold reduction of 1.29, 1.98 and 3.90, all P < 0.001 vs control). The growth effects of matched pleural fluid and cultured mesothelioma cells from the same patients did not differ significantly from unmatched pairs.

Conclusion: This 'proof-of-concept' study reveals potent biological capabilities of malignant pleural fluid in mesothelioma pathobiology.

© 2016 Asian Pacific Society of Respirology.

In plain English

This was a laboratory and mouse study. The authors used stored pleural fluid (fluid that builds up around the lungs) from 151 patients in the Australian Mesothelioma Biobank: 56 with malignant pleural mesothelioma, 60 with cancer that had spread to the pleura, and 35 with non-cancer conditions. They added the fluid, diluted to 30%, to mesothelioma cells grown in the laboratory. Fluid from mesothelioma patients significantly increased cell growth in all five cell lines tested, by median amounts of 1.50-fold to 2.92-fold over serum-free controls. It also significantly increased cell movement in all six lines tested. In mice with human mesothelioma tumours, tumours injected with the fluid were significantly larger than saline-injected tumours at day 13 (P = 0.0277). The fluid significantly reduced cell death caused by the chemotherapy drugs cisplatin and pemetrexed in three cell lines. Fluid from other cancers and from benign conditions also increased growth. The authors called this proof-of-concept work, warned that the results must not be over-extrapolated, and said the clinical relevance needs further research. The study did not examine asbestos exposure.

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) and animal (mouse) experiments using stored human pleural fluid samples; described by the authors as a proof-of-concept study
• Who was studied: 151 pleural fluid samples randomly selected from the Australian Mesothelioma Biobank cohort: 56 from patients with malignant pleural mesothelioma, 60 from metastatic pleural carcinoma and 35 from benign pleural diseases (including 2 benign asbestos pleural effusions). Seven established human mesothelioma cell lines, primary mesothelioma cells from three patients, and athymic nude mice were also used. Dates of sample collection are not given.
• Exposure: Mesothelioma cells were exposed to patients' pleural fluid diluted to 30%. In mice, the fluid was injected into tumours daily for six days. Cells were also treated with cisplatin and pemetrexed chemotherapy with or without the fluid. Asbestos exposure was not studied.
• Main results:
  • Pleural fluid from the 56 mesothelioma patients significantly increased mesothelioma cell growth in all five cell lines tested. Median increases over serum-free controls ranged from 1.50-fold (NO36) to 2.92-fold (JU77).
  • Mesothelioma pleural fluid significantly increased cell migration (closure of a scratch wound) in all six mesothelioma cell lines tested. Median wound closure ranged from 35.21% (STY51) to 68.8% (JU77), with all P values less than 0.0001.
  • In mice, tumours injected with mesothelioma pleural fluid (26 samples) grew significantly faster than saline-injected tumours during the injection period (P = 0.0002). At day 13 they were significantly larger than the saline control group (P = 0.0277).
  • Pleural fluid samples that caused more cell growth in the laboratory ('high inducers', n = 13) also made mouse tumours grow significantly faster than 'low inducer' samples (n = 13) and saline.
  • Adding mesothelioma pleural fluid significantly reduced cell death caused by cisplatin and pemetrexed in all three mesothelioma cell lines tested (LO68, JU77 and MSTO-211H).
  • Using cells and fluid from three mesothelioma patients, growth increased about twofold in all pairs. There was no significant difference between a patient's own fluid and another patient's fluid.
  • Pleural fluid from metastatic carcinomas (1.42 to 2.79-fold) and from benign effusions (1.27 to 2.2-fold) also increased mesothelioma cell growth over serum-free controls.
• The authors' conclusion: The authors concluded that malignant pleural fluid increased the growth of mesothelioma cells in the laboratory and in mice, promoted cell migration, and protected the cells from chemotherapy drugs. They said the clinical relevance of these properties warrants future research.
• Limitations the authors state:
  • The authors stated that the study has limitations and its results must not be over-extrapolated.
  • Pleural fluid is not required for mesothelioma to develop, since some patients never develop a malignant pleural effusion.
  • Whether removing the fluid improves survival or chemotherapy response was not tested and would need animal and human studies.
  • The clinical relevance of the chemotherapy-protection finding, seen only in the laboratory, requires investigation.

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: Mesothelioma, Pleural Effusion, Cisplatin, Pemetrexed (Alimta).

Related studies

• Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions — R. Thomas, H.M. Cheah, et al. (2016)
• Defect in recruiting effector memory CD8+ T-cells in malignant pleural effusions compared to normal pleural fluid — A. Scherpereel, B.D. Grigoriu, et al. (2013)
• 2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth — I. Gerogianni, E. Pitaraki, et al. (2019)
• Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin — J. Wörthmüller, V. Salicio, et al. (2019)
• Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines — M. Kitazono-Saitoh, Y. Takiguchi, et al. (2012)
• Dexamethasone alleviates pemetrexed-induced senescence in Non-Small-Cell Lung Cancer — H. Ge, J. Ke, et al. (2018)

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