Blockade of aquaporin 1 inhibits proliferation, motility, and metastatic potential of mesothelioma in vitro but not in an in vivo model.

Autor: Klebe S; Department of Anatomical Pathology, Flinders University, Adelaide, Bedford, SA 5042, Australia ; SA Pathology, Department of Surgical Pathology, Flinders Medical Centre, Adelaide, Bedford, SA 5042, Australia., Griggs K; Department of Anatomical Pathology, Flinders University, Adelaide, Bedford, SA 5042, Australia., Cheng Y; Asbestos Diseases Research Institute, Bernie Banton Centre, NSW 2139, Australia., Driml J; Department of Anatomical Pathology, Flinders University, Adelaide, Bedford, SA 5042, Australia., Henderson DW; Department of Anatomical Pathology, Flinders University, Adelaide, Bedford, SA 5042, Australia ; SA Pathology, Department of Surgical Pathology, Flinders Medical Centre, Adelaide, Bedford, SA 5042, Australia., Reid G; Asbestos Diseases Research Institute, Bernie Banton Centre, NSW 2139, Australia ; School of Medicine, University of Sydney, NSW 2006, Australia.
Jazyk: angličtina
Zdroj: Disease markers [Dis Markers] 2015; Vol. 2015, pp. 286719. Date of Electronic Publication: 2015 Mar 04.
DOI: 10.1155/2015/286719
Abstrakt: 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.
Databáze: MEDLINE
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