Human malignant pleural mesothelioma derived pleura fluid induces mesenchymal transition of benign pleural mesothelial cells

Background: Mesothelium plays a key role in the propagation and resolution of pleural inflammation and tissue repair. The potential of malignant pleural effusion fluid to induce mesothelial-to-mesenchymal transition (MMT) in human mesothelial cells is unknown. Aim: To examine the propensity of pleural cells to undergo MMT after exposure to malignant pleural mesothelioma induced pleural effusion fluid (MPEF). Methods: Gel contraction assay was performed by embedded benign (MeT5A) or mesothelioma cells (M14K: epithelioid, MSTO: biphasic, ZL34: sarcomatoid) in a mixture of neutralized rat tail collagen with either 10%RPMI media (Control) or 10%RPMI+MPEF. Contractility Index (CI) was determined by gel area measurements at 24, 48 and 72 hours. Results: A higher CI was observed in all cases when cells were exposed to 10%RPMI+MPEF as compared to 10%RPMI alone (p<0.001). More specifically, MeT5A differ at 24h (0.49±0.01, 0.60±0.01) and 48h (0.57±0.00, 0.63±0.01), M14K only at 24h (0.37±0.01, 0.49±0.02) while MSTO, ZL34 had significant differences in all timepoints. Conclusions: Here we report that benign as well as malignant mesothelial cells exhibit increased contractility when exposed to pleural fluid derived from malignant pleural mesothelioma pleural effusion. These findings may shed more light in the biology of the pleural space in the development of malignant pleural mesothelioma.