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MicroRNAs Present in Malignant Pleural Fluid Increase the Migration of Normal Mesothelial Cells In Vitro and May Help
Marta Marqués1, Mariona Pont1, Iván Hidalgo1
1Research Group of Cancer Biomarkers, Lleida Institute for Biomedical Research Dr. Pifarré Foundation (IRBLleida), Avda Alcalde Rovira Roure 80, 25198 Lleida, Spain.
Abstract:
The sensitivity of pleural fluid (PF) analyses for the diagnosis of malignant pleural effusions (MPEs) is low to moderate. Knowledge about the pathobiology and molecular characteristics of this condition is limited. In this study, the crosstalk between stromal cells and tumor cells was investigated in vitro in order to reveal factors that are present in PF which can mediate MPE formation and aid in discriminating between benign and malignant etiologies. Eighteen PF samples, in different proportions, were exposed in vitro to mesothelial MeT-5A cells to determine the biological effects on these cells. Treatment of normal mesothelial MeT-5A cells with malignant PF increased cell viability, proliferation, and migration, and activated different survival-related signaling pathways. We identified differentially expressed miRNAs in PF samples that could be responsible for these changes. Consistently, bioinformatics analysis revealed an enrichment of the discovered miRNAs in migration-related processes. Notably, the abundance of three miRNAs (miR-141-3p, miR-203a-3, and miR-200c-3p) correctly classified MPEs with false-negative cytological examination results, indicating the potential of these molecules for improving diagnosis. Malignant PF produces phenotypic and functional changes in normal mesothelial cells. These changes are partly mediated by certain miRNAs, which, in turn, could serve to differentiate malignant from benign effusions.
Insights
Malignant pleural effusions (MPEs) are hard to diagnose. Specific microRNAs (miRNAs) in pleural fluid can alter mesothelial cells, potentially improving MPE diagnosis and differentiating benign from malignant causes.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The diagnosis of malignant pleural effusions (MPEs) via pleural fluid (PF) analysis has limited sensitivity.
- Understanding the pathobiology and molecular features of MPEs remains a challenge.
Purpose of the Study:
- To investigate the crosstalk between stromal and tumor cells in vitro.
- To identify factors in PF that mediate MPE formation and distinguish benign from malignant effusions.
Main Methods:
- Normal mesothelial cells (MeT-5A) were treated with PF from MPE patients in vitro.
- Differential gene expression analysis, focusing on microRNAs (miRNAs), was performed.
- Bioinformatics analysis was used to identify biological processes associated with differentially expressed miRNAs.
Main Results:
- Malignant PF treatment enhanced mesothelial cell viability, proliferation, and migration.
- Specific miRNAs were identified as differentially expressed in malignant PF.
- Three miRNAs (miR-141-3p, miR-203a-3, and miR-200c-3p) showed potential for classifying MPEs, including those with negative cytology.
Conclusions:
- Malignant PF induces phenotypic and functional changes in normal mesothelial cells.
- These changes are partly mediated by specific miRNAs.
- The identified miRNAs may serve as diagnostic biomarkers to differentiate malignant from benign pleural effusions.
