Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
35750257
DOI
10.1016/j.ajpath.2022.05.009
PII: S0002-9440(22)00174-2
Knihovny.cz E-zdroje
- MeSH
- apoptóza MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty * patologie MeSH
- poly I-C farmakologie MeSH
- prostata patologie MeSH
- toll-like receptor 3 * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- poly I-C MeSH
- TLR3 protein, human MeSH Prohlížeč
- toll-like receptor 3 * MeSH
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.
Department of Cytokinetics Institute of Biophysics of Czech Academy of Sciences Brno Czech Republic
Department of Urology Experimental Urology Innsbruck Medical University Innsbruck Austria
Department of Urology University Hospital Olomouc Czech Republic
Department of Urology University Hospital Ostrava Czech Republic
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