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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00562613" target="_blank" >RIV/68081707:_____/22:00562613 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00159816:_____/22:00077682 RIV/00843989:_____/22:E0109729 RIV/00098892:_____/22:10157753 RIV/00216224:14310/22:00128751 RIV/61989592:15110/22:73615820

Výsledek na webu

<a href="https://doi.org/10.1016/j.ajpath.2022.05.009" target="_blank" >https://doi.org/10.1016/j.ajpath.2022.05.009</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ajpath.2022.05.009" target="_blank" >10.1016/j.ajpath.2022.05.009</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 interferonb, 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. (Am J Pathol 2022, 192: 1321e1335, https://doi.org/10.1016/j.ajpath.2022.05.009)

Název v anglickém jazyce

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

Popis výsledku anglicky

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 interferonb, 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. (Am J Pathol 2022, 192: 1321e1335, https://doi.org/10.1016/j.ajpath.2022.05.009)

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

American Journal of Pathology

ISSN

0002-9440

e-ISSN

1525-2191

Svazek periodika

192

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

1321-1335

Kód UT WoS článku

000859598300009

EID výsledku v databázi Scopus

2-s2.0-85137156103