Abstract
Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy. In MPM cells the amiloride sensitive sodium channel (ENaC) is expressed, however its role in cell migration is unknown.
Aim: Our aim was to investigate the role of ENaC inhibition on MPM cell migration during wound healing.
Materials and methods: The human cell lines MeT-5A (benign mesothelial cells), M14K (epithelioid MPM), MSTO (biphasic MPM) and ZL34 (sarcomatoid MPM) were used in this study. Cell migration was tested at 4 hrs on fibronectin (FN) and at 8 hrs on homologous cell derived extracellular matrix (ECM) coated plates. ENaC inhibition was done by amiloride (AM, 10-5M). Migration index (MI) was used as a measure of cell migration.
Results: The migration of MeT-5A (MI=0.06±0.01; p<0.001) and M14K (MI=0.09±0.01; p<0.005) cells were significantly lower than both MSTO (MI=0.22±0.01) and ZL34 (MI=0.59±0.03) cells on FN coated plates. Additionally, MSTO cell migration was significantly lower than ZL34 (p<0.001). On ECM coated plates, MeT-5A (MI=0.18±0.01) was significantly lower than MSTO (MI=0.33±0.01; p<0.01) and ZL34 (MI=0.90±0.02; p<0.001), while migration of M14K (MI=0.23±0.01) was significantly lower than MSTO (p<0.01) and ZL34 (p<0.001). Inhibition of ENaC with AM showed significant decrease of the cell migration in MeT-5A (p<0.05) and ZL34 (p<0.05) on FN coated plates. On ECM, the inhibitory effect of AM on cell migration was shown on MSTO (p<0.05) and ZL34 (p<0.05) cells.
Conclusion: ENaC inhibition differentially decreases the cell migration of normal mesothelial and MPM cells in a histological and substartum dependent manner.
- Copyright ©the authors 2016
