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

J 2022

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

MURESAN, Ximena M., Eva SLABÁKOVÁ, Jiřina PROCHÁZKOVÁ, Stanislav DRÁPELA, Radek FEDR et. al.

Basic information

Original name

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

Authors

Edition

American Journal of Pathology, Elsevier, 2022, 0002-9440

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.000

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.ajpath.2022.05.009

UT WoS

000859598300009

Keywords in English

prostate cancer; PCa; toll-like receptor; TLR3; resistance; chemotherapy; endocrine therapy

Abstract

V originále

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.

Links

EF16_025/0007381, research and development project

Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

EF18_046/0015974, research and development project

Name: Modernizace České infrastruktury pro integrativní strukturní biologii

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

MURESAN, Ximena M., Eva SLABÁKOVÁ, Jiřina PROCHÁZKOVÁ, Stanislav DRÁPELA, Radek FEDR, Markéta PÍCKOVÁ, Ondřej VACEK, Ráchel VÍCHOVÁ, Tereza SUCHÁNKOVÁ, Jan BOUCHAL, Daniela KÜRFÜRSTOVÁ, Milan KRÁL, Tereza HULÍNOVÁ, Radek P. SÝKORA, Vladimír ŠTUDENT, Václav HEJRET, Wytske M. VAN WEERDEN, Martin PUHR, Václav PUSTKA, David POTĚŠIL, Zbyněk ZDRÁHAL, Zoran CULIG and Karel SOUČEK. Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis. American Journal of Pathology. Elsevier, 2022, vol. 192, No 9, p. 1321-1335. ISSN 0002-9440. Available from: https://dx.doi.org/10.1016/j.ajpath.2022.05.009.

@article{2396650,
   author = {Muresan, Ximena M. and Slabáková, Eva and Procházková, Jiřina and Drápela, Stanislav and Fedr, Radek and Pícková, Markéta and Vacek, Ondřej and Víchová, Ráchel and Suchánková, Tereza and Bouchal, Jan and Kürfürstová, Daniela and Král, Milan and Hulínová, Tereza and Sýkora, Radek P. and Študent, Vladimír and Hejret, Václav and van Weerden, Wytske M. and Puhr, Martin and Pustka, Václav and Potěšil, David and Zdráhal, Zbyněk and Culig, Zoran and Souček, Karel},
   article_number = {9},
   doi = {http://dx.doi.org/10.1016/j.ajpath.2022.05.009},
   keywords = {prostate cancer; PCa; toll-like receptor; TLR3; resistance; chemotherapy; endocrine therapy},
   language = {eng},
   issn = {0002-9440},
   journal = {American Journal of Pathology},
   title = {Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis},
   url = {https://doi.org/10.1016/j.ajpath.2022.05.009},
   volume = {192},
   year = {2022}
}

TY  - JOUR
ID  - 2396650
AU  - Muresan, Ximena M. - Slabáková, Eva - Procházková, Jiřina - Drápela, Stanislav - Fedr, Radek - Pícková, Markéta - Vacek, Ondřej - Víchová, Ráchel - Suchánková, Tereza - Bouchal, Jan - Kürfürstová, Daniela - Král, Milan - Hulínová, Tereza - Sýkora, Radek P. - Študent, Vladimír - Hejret, Václav - van Weerden, Wytske M. - Puhr, Martin - Pustka, Václav - Potěšil, David - Zdráhal, Zbyněk - Culig, Zoran - Souček, Karel
PY  - 2022
TI  - Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis
JF  - American Journal of Pathology
VL  - 192
IS  - 9
SP  - 1321-1335
EP  - 1321-1335
PB  - Elsevier
SN  - 00029440
KW  - prostate cancer
KW  - PCa
KW  - toll-like receptor
KW  - TLR3
KW  - resistance
KW  - chemotherapy
KW  - endocrine therapy
UR  - https://doi.org/10.1016/j.ajpath.2022.05.009
N2  - 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.
ER  -

MURESAN, Ximena M., Eva SLABÁKOVÁ, Jiřina PROCHÁZKOVÁ, Stanislav DRÁPELA, Radek FEDR, Markéta PÍCKOVÁ, Ondřej VACEK, Ráchel VÍCHOVÁ, Tereza SUCHÁNKOVÁ, Jan BOUCHAL, Daniela KÜRFÜRSTOVÁ, Milan KRÁL, Tereza HULÍNOVÁ, Radek P. SÝKORA, Vladimír ŠTUDENT, Václav HEJRET, Wytske M. VAN WEERDEN, Martin PUHR, Václav PUSTKA, David POTĚŠIL, Zbyněk ZDRÁHAL, Zoran CULIG and Karel SOUČEK. Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis. \textit{American Journal of Pathology}. Elsevier, 2022, vol.~192, No~9, p.~1321-1335. ISSN~0002-9440. Available from: https://dx.doi.org/10.1016/j.ajpath.2022.05.009.

Detailed Information on Publication Record