Abstract
BackgroundThe aquaporins (AQPs), water channel proteins, are known playing a major role in transcellular and transepithelial water movement; they also exhibit several properties related to tumor development. The aim of the present study is to elucidate whether the expression of AQP5 is a strong prognostic biomarker for prostate cancer, and the potential role in the progression of prostate cancer cells.MethodsAQP5 expression was measured in 60 prostate cancer tissues and cells (both PC-3 and LNCaP) by immunohistochemistry and immunofluorescence assay. AQP5 gene amplification was detected with FISH (fluorescence in situ hybridization). Proliferation and migration of cells and AQP5 siRNA cells were detected with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Boyden chambers. Circulating tumor cells (CTCs) were detected by imFISH staining (CEP8-CD45-DAPI) assay.ResultsThe results showed that in 60 tumor specimens, 19 (31.7%) patients showed high level of AQP5 expression, while 30 (50.0%) showed a moderate, intermediate level of staining, and 11 (18.3%) showed an absence of AQP5 staining, respectively. High-expression of AQP5 protein frequently accompanied gene amplification detection with FISH. The AQP5 over-expression was also associated with TNM stage (P = 0.042), and lymph node metastasis (P = 0.001). The relationships between age or tumor size with the expression of AQP5 were not significant (P > 0.05). A positive correlation between the number of CTCs and AQP5 expression (P < 0.05) was demonstrated. In addition, patients who were negative for AQP5 had superior cumulative survival rate than those who were positive for it. Over-expression of AQP5 protein was also found in prostate cancer cells and cell proliferation and migration were significantly attenuated by AQP5-siRNA.ConclusionsWe concluded that AQP5 in prostate cancer was an independent prognostic indicator. AQP5 over-expression was likely to play a role in cell growth and metastasis. These conclusions suggest that AQP5 may be an effective therapeutic target for prostate cancer.
Highlights
The aquaporins (AQPs), water channel proteins, are known playing a major role in transcellular and transepithelial water movement; they exhibit several properties related to tumor development
In 19/ 60 (31.7%) patients, AQP5 expression was strong and in 30/60 (50.0%) patients AQP5 expression was moderate in the cancer group
To further determine AQP5 expression, prostate tissue was stained with fluorescence immunostaining and analyzed by confocal microscopy
Summary
The aquaporins (AQPs), water channel proteins, are known playing a major role in transcellular and transepithelial water movement; they exhibit several properties related to tumor development. The aim of the present study is to elucidate whether the expression of AQP5 is a strong prognostic biomarker for prostate cancer, and the potential role in the progression of prostate cancer cells. Prostate cancer (PCa) is the second most frequent cause of cancer-related deaths among males in the USA [1]. Despite the widespread presence of clinically insignificant tumors in elderly men, PCa commonly has an aggressive phenotype that requires prompt intervention [2]. Water can permeate the plasma membrane by simple diffusion, but bulk water flow is mediated by a channel mechanism through aquaporin (AQP) enzymes [3]. AQPs belong to a family of water-transporting proteins. 13 members of the AQPs have been identified and can be subdivided into two groups on the basis of their permeability: AQP1, 2, 4, 5 and 8 are water-selective transporters, while AQP3, 7, 9 and 10, termed aquaglyceroporins, transport water as well as glycerol and other small solutes [4,5,6]
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