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Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study

Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of...

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Autores principales: Neuhaus, Jochen, Schiffer, Eric, Mannello, Ferdinando, Horn, Lars-Christian, Ganzer, Roman, Stolzenburg, Jens-Uwe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454889/
https://www.ncbi.nlm.nih.gov/pubmed/28471417
http://dx.doi.org/10.3390/ijms18050976
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author Neuhaus, Jochen
Schiffer, Eric
Mannello, Ferdinando
Horn, Lars-Christian
Ganzer, Roman
Stolzenburg, Jens-Uwe
author_facet Neuhaus, Jochen
Schiffer, Eric
Mannello, Ferdinando
Horn, Lars-Christian
Ganzer, Roman
Stolzenburg, Jens-Uwe
author_sort Neuhaus, Jochen
collection PubMed
description Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin 1 and 2, representing endpoints of the ejaculate liquefaction. Here we identified proteases putatively involved in PCa specific protein cleavage, and examined gene expression and tissue protein levels, jointly with cell localization in normal prostate (nP), benign prostate hyperplasia (BPH), seminal vesicles and PCa using qPCR, Western blotting and confocal laser scanning microscopy. We found differential gene expression of chymase (CMA1), matrix metalloproteinases (MMP3, MMP7), and upregulation of MMP14 and tissue inhibitors (TIMP1 and TIMP2) in BPH. In contrast tissue protein levels of MMP14 were downregulated in PCa. MMP3/TIMP1 and MMP7/TIMP1 ratios were decreased in BPH. In seminal vesicles, we found low-level expression of most proteases and, interestingly, we also detected TIMP1 and low levels of TIMP2. We conclude that MMP3 and MMP7 activity is different in PCa compared to BPH due to fine regulation by their inhibitor TIMP1. Our findings support the concept of seminal plasma biomarkers as non-invasive tool for PCa detection and risk stratification.
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spelling pubmed-54548892017-06-08 Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study Neuhaus, Jochen Schiffer, Eric Mannello, Ferdinando Horn, Lars-Christian Ganzer, Roman Stolzenburg, Jens-Uwe Int J Mol Sci Article Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin 1 and 2, representing endpoints of the ejaculate liquefaction. Here we identified proteases putatively involved in PCa specific protein cleavage, and examined gene expression and tissue protein levels, jointly with cell localization in normal prostate (nP), benign prostate hyperplasia (BPH), seminal vesicles and PCa using qPCR, Western blotting and confocal laser scanning microscopy. We found differential gene expression of chymase (CMA1), matrix metalloproteinases (MMP3, MMP7), and upregulation of MMP14 and tissue inhibitors (TIMP1 and TIMP2) in BPH. In contrast tissue protein levels of MMP14 were downregulated in PCa. MMP3/TIMP1 and MMP7/TIMP1 ratios were decreased in BPH. In seminal vesicles, we found low-level expression of most proteases and, interestingly, we also detected TIMP1 and low levels of TIMP2. We conclude that MMP3 and MMP7 activity is different in PCa compared to BPH due to fine regulation by their inhibitor TIMP1. Our findings support the concept of seminal plasma biomarkers as non-invasive tool for PCa detection and risk stratification. MDPI 2017-05-04 /pmc/articles/PMC5454889/ /pubmed/28471417 http://dx.doi.org/10.3390/ijms18050976 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Neuhaus, Jochen
Schiffer, Eric
Mannello, Ferdinando
Horn, Lars-Christian
Ganzer, Roman
Stolzenburg, Jens-Uwe
Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study
title Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study
title_full Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study
title_fullStr Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study
title_full_unstemmed Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study
title_short Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study
title_sort protease expression levels in prostate cancer tissue can explain prostate cancer-associated seminal biomarkers—an explorative concept study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454889/
https://www.ncbi.nlm.nih.gov/pubmed/28471417
http://dx.doi.org/10.3390/ijms18050976
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