Pleural Fluid Has Pro-Growth Biological Properties Which Enable Cancer Cell Proliferation

Our plain-English summary of Pleural Fluid Has Pro-Growth Biological Properties Which Enable Cancer Cell Proliferation, by R. Asciak, N.I. Kanellakis, X. Yao, et al (Frontiers in Oncology, 2021).

The study

• Authors: R. Asciak, N.I. Kanellakis, X. Yao, M. Abd Hamid, R.M. Mercer, M. Hassan, E.O. Bedawi, M. Dobson, P. Fsadni, S. Montefort, T. Dong, N.M. Rahman, I. Psallidas
• Journal: Frontiers in Oncology
• Published: 2021;11:658395
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Patients with malignant pleural mesothelioma (MPM) or pleural metastases often present with malignant pleural effusion (MPE). This study aimed to analyze the effect of pleural fluid on cancer cells.

Materials And Methods: Established patient-derived cancer cell cultures derived from MPE (MPM, breast carcinoma, lung adenocarcinoma) were seeded in 100% pleural fluid (exudate MPM MPE, transudate MPE, non-MPE transudate fluid) and proliferation was monitored. In addition, the establishment of new MPM cell cultures, derived from MPE specimens, was attempted by seeding the cells in 100% MPE fluid.

Results: All established cancer cell cultures proliferated with similar growth rates in the different types of pleural fluid. Primary MPM cell culture success was similar with MPE fluid as with full culture medium.

Conclusions: Pleural fluid alone is adequate for cancer cell proliferation in vitro, regardless of the source of pleural fluid. These results support the hypothesis that pleural fluid has important pro-growth biological properties, but the mechanisms for this effect are unclear and likely not malignant effusion specific.

Copyright © 2021 Asciak, Kanellakis, Yao, Abd Hamid, Mercer, Hassan, Bedawi, Dobson, Fsadni, Montefort, Dong, Rahman and Psallidas.

In plain English

This laboratory study grew cancer cells in dishes. It did not examine asbestos exposure. The authors tested whether pleural fluid (fluid that collects around the lung), with nothing else added, could support the growth of cancer cells taken from patients. They used cell cultures from five patients with malignant pleural mesothelioma, one with breast carcinoma and one with lung adenocarcinoma. Mesothelioma cells kept only in mesothelioma effusion fluid covered more of the dish over time. Mesothelioma cells grew at similar rates in protein-rich (exudate) fluid from a mesothelioma patient and in low-protein (transudate) fluid from a lung adenocarcinoma patient. Breast and lung cancer cells also grew in pleural fluid alone. Cancer cells also grew in fluid from a patient with heart failure. When new mesothelioma cultures were started from 6 effusion samples, 3 of 6 succeeded in both effusion fluid and standard medium, and 2 of 6 failed in both. The authors concluded that any form of human pleural fluid appeared to have this effect, and that the mechanism was unclear. They noted that the fluid's thickness made growth hard to measure.

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 using patient-derived cancer cells grown in 100% pleural fluid
• Who was studied: Established patient-derived cell cultures: five malignant pleural mesothelioma (MPM) cultures (MESO-163, MESO-031 and MESO-027 epithelioid; MESO-174 and MESO-024 biphasic), one breast carcinoma (BRST-156) and one lung adenocarcinoma (LNG-183). A commercial biphasic MPM cell line (CRL-2081, MSTO-211H) was used as a control. Six further MPM effusion samples were used for new primary cultures. Fluid came from patients in the Oxford Radcliffe Pleural Biobank, Oxford, United Kingdom.
• Exposure: No asbestos or fiber exposure was studied. The cells were exposed to three kinds of 100% pleural fluid: exudate MPM malignant pleural effusion fluid, transudate malignant pleural effusion fluid (from metastatic lung adenocarcinoma), and non-malignant transudate fluid from a patient with heart failure.
• Main results:
  • Cells from the established MPM culture MESO-163, grown only in exudate MPM effusion fluid, showed increasing confluence (coverage of the well) over 12 days.
  • MPM cells showed similar growth rates in exudative MPM effusion fluid and in transudative malignant effusion fluid.
  • Breast carcinoma and lung adenocarcinoma cells also proliferated in 100% pleural fluid alone.
  • Cancer cells proliferated in non-malignant transudate pleural fluid from a patient with heart failure.
  • Proliferation was lower with transudate malignant effusion fluid for MESO-163 and with heart failure transudate for MESO-027. No single fluid type clearly reduced proliferation across all cell cultures.
  • There was no significant difference in cell morphology or cell size between the different pleural fluid types.
  • New primary MPM cultures were attempted from 6 effusion samples. In 3 of 6 (50%), culture succeeded in both effusion fluid and standard medium. In 1 of 6 (16.7%), culture failed from the start in standard medium and failed beyond passage 1 in pleural fluid. In 2 of 6 (33.3%), culture failed in both.
• The authors' conclusion: The authors concluded that cancer cells could survive and proliferate in 100% pleural fluid. They wrote that any form of human pleural fluid (malignant, non-malignant, transudate, exudate) appears to have this effect, although the mechanism is unclear. They called for prospective clinical studies and further translational studies.
• Limitations the authors state:
  • The thickness (viscosity) of pleural fluid limited the use of the usual methods for measuring cell proliferation and viability, so the authors combined live images, a luminescence assay and confluence calculations.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleural Effusion, Carcinoma, Lung Adenocarcinoma, Exudate.

Related studies

• Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments — N.I. Kanellakis, R. Asciak, et al. (2020)
• The Association Between Pleural Fluid Exposure and Survival in Pleural Mesothelioma — R. Asciak, N.I. Kanellakis, et al. (2021)
• Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth — D.A. Altomare, H. You, et al. (2005)
• Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma — E.R. Gamazon, M.R. Trendowski, et al. (2018)
• Significance of cell proliferation markers (Minichromosome maintenance protein 7, topoisomerase IIalpha and Ki-67) in cavital fluid cytology: can we differentiate reactive mesothelial cells from malignant cells? — F. Kimura, J. Kawamura, et al. (2010)
• KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos — I.Y. Adamson, J. Bakowska (2001)

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