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Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis

XM. Muresan, E. Slabáková, J. Procházková, S. Drápela, R. Fedr, M. Pícková, O. Vacek, R. Víchová, T. Suchánková, J. Bouchal, D. Kürfürstová, M. Král, T. Hulínová, RP. Sýkora, V. Študent, V. Hejret, WM. van Weerden, M. Puhr, V. Pustka, D. Potěšil,...

. 2022 ; 192 (9) : 1321-1335. [pub] 20220622

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22024502

Toll-like receptor 3 (TLR3) is an endosomal receptor expressed in several immune and epithelial cells. Recent studies have highlighted its expression also in solid tumors, including prostate cancer (PCa), and have described its role primarily in the proinflammatory response and induction of apoptosis. It is up-regulated in some castration-resistant prostate cancers. However, the role of TLR3 in prostate cancer progression remains largely unknown. The current study experimentally demonstrated that exogenous TLR3 activation in PCa cell lines leads to a significant induction of secretion of the cytokines IL-6, IL-8, and interferon-β, depending on the model and chemoresistance status. Transcriptomic analysis of TLR3-overexpressing cells revealed a functional program that is enriched for genes involved in the regulation of cell motility, migration, and tumor invasiveness. Increased motility, migration, and invasion in TLR3-overexpressing cell line were confirmed by several in vitro assays and using an orthotopic prostate xenograft model in vivo. Furthermore, TLR3-ligand induced apoptosis via cleavage of caspase-3/7 and poly (ADP-ribose) polymerase, predominantly in TLR3-overexpressing cells. These results indicate that TLR3 may be involved in prostate cancer progression and metastasis; however, it might also represent an Achilles heel of PCa, which can be exploited for targeted therapy.

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$a Muresan, Ximena M $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic
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$a Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis / $c XM. Muresan, E. Slabáková, J. Procházková, S. Drápela, R. Fedr, M. Pícková, O. Vacek, R. Víchová, T. Suchánková, J. Bouchal, D. Kürfürstová, M. Král, T. Hulínová, RP. Sýkora, V. Študent, V. Hejret, WM. van Weerden, M. Puhr, V. Pustka, D. Potěšil, Z. Zdráhal, Z. Culig, K. Souček
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$a Toll-like receptor 3 (TLR3) is an endosomal receptor expressed in several immune and epithelial cells. Recent studies have highlighted its expression also in solid tumors, including prostate cancer (PCa), and have described its role primarily in the proinflammatory response and induction of apoptosis. It is up-regulated in some castration-resistant prostate cancers. However, the role of TLR3 in prostate cancer progression remains largely unknown. The current study experimentally demonstrated that exogenous TLR3 activation in PCa cell lines leads to a significant induction of secretion of the cytokines IL-6, IL-8, and interferon-β, depending on the model and chemoresistance status. Transcriptomic analysis of TLR3-overexpressing cells revealed a functional program that is enriched for genes involved in the regulation of cell motility, migration, and tumor invasiveness. Increased motility, migration, and invasion in TLR3-overexpressing cell line were confirmed by several in vitro assays and using an orthotopic prostate xenograft model in vivo. Furthermore, TLR3-ligand induced apoptosis via cleavage of caspase-3/7 and poly (ADP-ribose) polymerase, predominantly in TLR3-overexpressing cells. These results indicate that TLR3 may be involved in prostate cancer progression and metastasis; however, it might also represent an Achilles heel of PCa, which can be exploited for targeted therapy.
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$a Slabáková, Eva $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic
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$a Procházková, Jiřina $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic
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$a Drápela, Stanislav $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic $7 xx0280838
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$a Fedr, Radek $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic
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$a Pícková, Markéta $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
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$a Vacek, Ondřej $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
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$a Víchová, Ráchel $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic
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$a Suchánková, Tereza $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic
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$a Bouchal, Jan $u Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
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$a Kürfürstová, Daniela $u Department of Urology, University Hospital, Olomouc, Czech Republic
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$a Král, Milan $u Department of Urology, University Hospital, Olomouc, Czech Republic
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$a Hulínová, Tereza $u Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic; Department of Clinical and Molecular Pathology, University Hospital, Ostrava, Czech Republic
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$a Sýkora, Radek P $u Department of Urology, University Hospital, Ostrava, Czech Republic
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$a Študent, Vladimír $u Department of Urology, University Hospital, Olomouc, Czech Republic
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$a Hejret, Václav $u Bioinformatics Core Facility Central European Institute of Technology, Masaryk University, Brno, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic
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$a van Weerden, Wytske M $u Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
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$a Puhr, Martin $u Proteomics Core Facility Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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$a Pustka, Václav $u Department of Urology, Experimental Urology, Innsbruck Medical University, Innsbruck, Austria
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$a Potěšil, David $u Department of Urology, Experimental Urology, Innsbruck Medical University, Innsbruck, Austria
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$a Zdráhal, Zbyněk $u Department of Urology, Experimental Urology, Innsbruck Medical University, Innsbruck, Austria
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$a Culig, Zoran $u International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic; Proteomics Core Facility Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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$a Souček, Karel $u Department of Cytokinetics, Institute of Biophysics of Czech Academy of Sciences, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic. Electronic address: ksoucek@ibp.cz
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