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Disease Markers
Volume 2015 (2015), Article ID 286719, 9 pages
http://dx.doi.org/10.1155/2015/286719
Research Article

Blockade of Aquaporin 1 Inhibits Proliferation, Motility, and Metastatic Potential of Mesothelioma In Vitro but not in an In Vivo Model

1Department of Anatomical Pathology, Flinders University, Adelaide, Bedford, SA 5042, Australia
2SA Pathology, Department of Surgical Pathology, Flinders Medical Centre, Adelaide, Bedford, SA 5042, Australia
3Asbestos Diseases Research Institute, Bernie Banton Centre, NSW 2139, Australia
4School of Medicine, University of Sydney, NSW 2006, Australia

Received 14 December 2014; Accepted 16 February 2015

Academic Editor: Marco E. M. Peluso

Copyright © 2015 Sonja Klebe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly the pleura. It is related to asbestos exposure and has a poor prognosis. MM has a long latency period, and incidence is predicted to remain stable or increase until 2020. Currently, no biomarkers for a specific targeted therapy are available. Previously, we observed that expression of aquaporin 1 (AQP1) was an indicator of prognosis in two independent cohorts. Here we determine whether AQP1 inhibition has therapeutic potential in the treatment of MM. Methods. Functional studies were performed with H226 cells and primary MM cells harvested from pleural effusions. AQP1 expression and mesothelial phenotype was determined by immunohistochemistry. AQP1 function was inhibited by a pharmacological blocker (AqB050) or AQP1-specific siRNA. Cell proliferation, migration, and anchorage-independent cell growth were assessed. A nude mouse heterotopic xenograft model of MM was utilised for the in vivo studies. Results. Inhibition of AQP1 significantly decreases cell proliferation, metastatic potential, and motility without inducing nonspecific cytotoxicity or increasing apoptosis. In vivo blockade of AQP1 had no biologically significant effect on growth of established tumours. Conclusions. Targeted blockade of AQP1 restricts MM growth and migration in vitro. Further work is warranted to fully evaluate treatment potential in vivo.