Abstract
Aim: Malignant pleural mesothelioma (MPM) is an aggresive malignancy. Recently the role of water channels in MPM has started being investigated and patients with aquaporin-1 (AQP1) have favorable survival. In MPM the amiloride sensitive sodium channel (EnaC) is also expressed. Our aim was to investigate the role of AQP1 and ENaC in cell adhesion in mesothelial cells and in MPM cells.
Methods: The human cell lines Met5A (benign mesothelial cells), M14K (epithelioid mesothelioma), ZL35 (sarcomatoid mesothelioma) were used. Cell adhesion was tested in fibronectin coated plates and in homologous cell derived extracellular matrix coated plates. In some experiments AQP1 inhibition or ENaC inhibition was performed with HgCl2 and amiloride respectively.
Results: Inhibition of AQP1 resulted in significant decrease of Met5A and M14K cell adhesion irrispective of plate coating (p<0.05 and p<0.001 respectively). In ZL35 no difference was observed. ENaC inhibition on fibronectin substrate resulted in significant reduction of M14K cell adhesion (p<0.001). Lastly, in homologous cell derived extracellular matrix coated plates EnaC inhibition significantly reduced the adhesion of all 3 cell types (p<0.001).
Conclusion: In cell adhesion of mesothelioma cells, AQP1 inhibition is cell-type dependent while EnaC inhibition is cell-type and extracellular matrix-type dependent. These results render AQP1 and/or EnaC drug targeting worth investigating in MPM pathobiology.
- Copyright ©ERS 2015