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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89041 |
| Date | 16 January 2024 |
| Creators | Neuhaus, Jochen, Schiffer, Eric, Mannello, Ferdinando, Horn, Lars-Christian, Ganzer, Roman, Stolzenburg, Jens-Uwe |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 976 |
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