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Int J Mol Sci. 2017 May 4;18(5). pii: E976. doi: 10.3390/ijms18050976.

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

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Department of Urology, Research Laboratory, University of Leipzig, Liebigstraße 19, 04103 Leipzig, Germany.
Numares AG, Regensburg, Am BioPark 9, 93053 Regensburg, Germany.
Department of Biomolecular Sciences, University "Carlo Bo", Via O. Ubaldini 7, 61029 Urbino (PU), Italy.
Institute of Pathology, University Hospital Leipzig, Liebigstraße 24, 04103 Leipzig, Germany.
Department of Urology, University Hospital Leipzig, Liebigstraße 20, 04103 Leipzig, Germany.
Department of Urology, University Hospital Leipzig, Liebigstraße 20, 04103 Leipzig, Germany.


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.


Western blotting; confocal laser scanning microscopy; matrix metalloproteinase (MMP); qPCR; seminal plasma biomarkers; tissue inhibitor of MMP (TIMP)

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