Expression, Localisation and Potential Significance of Aquaporins in Benign and Malignant Human Prostate Tissue

Johannes Bründl, Sabine Wallinger, Johannes Breyer, Florian Weber, Matthias Evert, Nikolaos Theodoros Georgopoulos, Bernd Rosenhammer, Maximilian Burger, Wolfgang Otto, Peter Rubenwolf

Research output: Contribution to journalArticle

Abstract

Background: To study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue. Methods: The AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-ΔCT method and correlated to clinicopathological parameters. Results: Transcripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (ρ = - 0.354; p = 0.013), D'Amico risk stratification (ρ = - 0.336; p = 0.012), ISUP grade (ρ = - 0.321; p = 0.017) and Gleason score (ρ = - 0.342; p = 0.011). Conclusions: This is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.

LanguageEnglish
Article number75
JournalBMC Urology
Volume18
Issue number1
DOIs
Publication statusPublished - 3 Sep 2018

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Aquaporins
Prostate
Prostatic Neoplasms
Cell Line
Prostatic Hyperplasia
Reverse Transcriptase Polymerase Chain Reaction
Fluorescence Microscopy
Neoplasms
Proteins
Immunohistochemistry
Messenger RNA
Neoplasm Grading
Gene Expression

Cite this

Bründl, Johannes ; Wallinger, Sabine ; Breyer, Johannes ; Weber, Florian ; Evert, Matthias ; Georgopoulos, Nikolaos Theodoros ; Rosenhammer, Bernd ; Burger, Maximilian ; Otto, Wolfgang ; Rubenwolf, Peter. / Expression, Localisation and Potential Significance of Aquaporins in Benign and Malignant Human Prostate Tissue. In: BMC Urology. 2018 ; Vol. 18, No. 1.
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title = "Expression, Localisation and Potential Significance of Aquaporins in Benign and Malignant Human Prostate Tissue",
abstract = "Background: To study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue. Methods: The AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-ΔCT method and correlated to clinicopathological parameters. Results: Transcripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (ρ = - 0.354; p = 0.013), D'Amico risk stratification (ρ = - 0.336; p = 0.012), ISUP grade (ρ = - 0.321; p = 0.017) and Gleason score (ρ = - 0.342; p = 0.011). Conclusions: This is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.",
keywords = "Aquaporins, Human prostate, Prostate cancer, Prostate cancer cell lines",
author = "Johannes Br{\"u}ndl and Sabine Wallinger and Johannes Breyer and Florian Weber and Matthias Evert and Georgopoulos, {Nikolaos Theodoros} and Bernd Rosenhammer and Maximilian Burger and Wolfgang Otto and Peter Rubenwolf",
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Bründl, J, Wallinger, S, Breyer, J, Weber, F, Evert, M, Georgopoulos, NT, Rosenhammer, B, Burger, M, Otto, W & Rubenwolf, P 2018, 'Expression, Localisation and Potential Significance of Aquaporins in Benign and Malignant Human Prostate Tissue', BMC Urology, vol. 18, no. 1, 75. https://doi.org/10.1186/s12894-018-0391-y

Expression, Localisation and Potential Significance of Aquaporins in Benign and Malignant Human Prostate Tissue. / Bründl, Johannes; Wallinger, Sabine; Breyer, Johannes; Weber, Florian; Evert, Matthias; Georgopoulos, Nikolaos Theodoros; Rosenhammer, Bernd; Burger, Maximilian; Otto, Wolfgang; Rubenwolf, Peter.

In: BMC Urology, Vol. 18, No. 1, 75, 03.09.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expression, Localisation and Potential Significance of Aquaporins in Benign and Malignant Human Prostate Tissue

AU - Bründl, Johannes

AU - Wallinger, Sabine

AU - Breyer, Johannes

AU - Weber, Florian

AU - Evert, Matthias

AU - Georgopoulos, Nikolaos Theodoros

AU - Rosenhammer, Bernd

AU - Burger, Maximilian

AU - Otto, Wolfgang

AU - Rubenwolf, Peter

PY - 2018/9/3

Y1 - 2018/9/3

N2 - Background: To study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue. Methods: The AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-ΔCT method and correlated to clinicopathological parameters. Results: Transcripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (ρ = - 0.354; p = 0.013), D'Amico risk stratification (ρ = - 0.336; p = 0.012), ISUP grade (ρ = - 0.321; p = 0.017) and Gleason score (ρ = - 0.342; p = 0.011). Conclusions: This is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.

AB - Background: To study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue. Methods: The AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-ΔCT method and correlated to clinicopathological parameters. Results: Transcripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (ρ = - 0.354; p = 0.013), D'Amico risk stratification (ρ = - 0.336; p = 0.012), ISUP grade (ρ = - 0.321; p = 0.017) and Gleason score (ρ = - 0.342; p = 0.011). Conclusions: This is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.

KW - Aquaporins

KW - Human prostate

KW - Prostate cancer

KW - Prostate cancer cell lines

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U2 - 10.1186/s12894-018-0391-y

DO - 10.1186/s12894-018-0391-y

M3 - Article

VL - 18

JO - BMC Urology

T2 - BMC Urology

JF - BMC Urology

SN - 1471-2490

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ER -