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Open Access Research article

Loss of aquaporin-4 expression and putative function in non-small cell lung cancer

Arne Warth1*, Thomas Muley2, Michael Meister2, Esther Herpel1, Anita Pathil3, Hans Hoffmann4, Philipp A Schnabel1, Christian Bender5, Andreas Buness5, Peter Schirmacher1 and Ruprecht Kuner5

Author Affiliations

1 Institute of Pathology, University Hospital Heidelberg, Germany

2 Translational Research Unit, Thoraxklinik Heidelberg, Germany

3 Department of Internal Medicine IV, University Hospital Heidelberg, Germany

4 Department of Thoracic Surgery, Thoraxklinik Heidelberg, Germany

5 Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany

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BMC Cancer 2011, 11:161  doi:10.1186/1471-2407-11-161

Published: 6 May 2011

Abstract

Background

Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs.

Methods

We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry.

Results

Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue.

Conclusions

Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets.