Abstract
Purpose
To study the expression, localization and potential clinical significance of aquaporin water channels both in well-established urothelial cancer (UC) cell lines and in human bladder carcinoma specimens of different stages and grades and to discuss the clinical relevance of the findings.
Methods
AQP transcript and protein expression by RT4, RT112 and T24 UC cell lines was investigated using reverse transcriptase polymerase chain reaction and immunofluorescence labelling. Immunohistochemistry (IHC) was used to assess AQP protein expression in 94 UC specimens of various grades and stages.
Results
AQP3 and 9 transcripts were expressed in low-grade RT4 and RT112, but not in high-grade T24 cells. By contrast, AQP4 mRNA was absent in RT4, but expressed by RT112 and T24. Transcripts for AQP7 and 11 were detected in all three UC cell lines. Immunofluorescence microscopy confirmed the expression of AQP3, 4 and 7 at the protein level. By IHC, AQP3 was shown to be intensely expressed by 86 %, 66 % and 33 % of specimens of stage pTa, pT1 and pT2 tumours, respectively (p < 0.001). Whereas 100 % of G1 tumours were positive, only 73 % and 55 % of G2 and G3 tumours were found to express AQP3 (p = 0.004).
Conclusions
This is the first study to demonstrate that several AQPs are expressed in UC. Our results indicate that there is a correlation between AQP3 protein expression and tumour stage and grade, with AQP3 expression being reduced or lost in tumours of higher grade and stage. Taken together with the available evidence from other studies, we conclude that AQPs may play a role in the progression of UC and, in particular, that this could be of prognostic value.
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Acknowledgments
The authors wish to thank Professor Jenny Southgate at the Jack Birch Unit of Molecular Carcinogenesis (Department of Biology, University of York, UK) for helpful discussions during the preparation of the manuscript and acknowledge Professor Southgate’s valuable contribution to the in vitro experimental work. which was carried out in her laboratory. Peter C. Rubenwolf was in receipt of a clinical research fellowship from the Deutsche Forschungsgemeinschaft. The study was partly funded by a research grant from Yorkshire Kidney Research Fund.
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The authors declare that they have no conflict of interest.
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Rubenwolf, P.C., Otto, W., Denzinger, S. et al. Expression of aquaporin water channels in human urothelial carcinoma: correlation of AQP3 expression with tumour grade and stage. World J Urol 32, 991–997 (2014). https://doi.org/10.1007/s00345-013-1153-9
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DOI: https://doi.org/10.1007/s00345-013-1153-9