Modulation of aquaporin 1 function alters proliferation of malignant mesothelial cells

Abstract

<h3>Background</h3> Malignant mesothelioma (MM) is an aggressive tumour of serosal membranes with a poor prognosis. We have identified aquaporin 1 (AQP1) as a significant prognostic marker. <h3>Aims</h3> To investigate if expression levels of AQP1 correlate with proliferation of MM cells and if alteration of AQP1 function by pharmacological blockers and siRNA cell inhibits cell proliferation <i>in vitro</i>. <h3>Methods</h3> MM cell lines (H28, H2052, 211H, H226 and H2452) and normal mesothelial cells (MET5A) obtained from the ATCC and primary MM cells harvested from malignant pleural effusions were used. AQP1 expression was determined by immunohisto-chemistry (IHC) and mesothelial phenotype confirmed. Cell proliferation was measured with and without altered AQP1 channel function using the MTS assay. <h3>Results</h3> AQP1-positive cell lines (H226 and H28) and patient-derived MM cells with high AQP1 expression had overall higher proliferation rates than the AQP1 negative cells (H2052, 211H, H2452 and Met5A). AQP1 modulation by pharmacological agents from a custom synthetic chemical library can decrease cell proliferation without inducing cytotoxicity or increasing apoptosis. <h3>Conclusions</h3> AQP1 is a prognostic marker for MM and modulation of AQP1 function can alter MM cell proliferation. This has treatment potential. AQP1 inhibition by siRNA will further clarify the molecular mechanism leading to specific AQP1 modulation.