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Toll-like receptor agonists induce inflammation and cell death in a model of head and neck squamous cell carcinomas

Rydberg, Camilla; Månsson, Anne LU ; Uddman, Rolf LU ; Riesbeck, Kristian LU and Cardell, Lars-Olaf (2009) In Immunology 128(1). p.600-611
Abstract
P>Toll-like receptors (TLRs) are increasingly implicated in the pathogenesis of cancer. The present study describes TLR expression and function in healthy and malignant airway epithelial cells. The squamous cell carcinoma cell line Detroit-562 was compared with the healthy bronchial epithelial cell line NL-20 and primary human nasal epithelial cells (HNECs). TLR2, TLR3 and TLR5 were present in primary head and neck squamous cell carcinomas (HNSCCs). Consistent with this, Detroit-562 expressed TLR2, TLR3 and TLR5, whereas NL-20 expressed mainly TLR3 and HNECs expressed TLR2-5. In Detroit-562, Pam(3)CSK(4), poly(I:C) and flagellin, ligands for TLR2, TLR3 and TLR5, respectively, induced an up-regulation of intercellular adhesion molecule 1... (More)
P>Toll-like receptors (TLRs) are increasingly implicated in the pathogenesis of cancer. The present study describes TLR expression and function in healthy and malignant airway epithelial cells. The squamous cell carcinoma cell line Detroit-562 was compared with the healthy bronchial epithelial cell line NL-20 and primary human nasal epithelial cells (HNECs). TLR2, TLR3 and TLR5 were present in primary head and neck squamous cell carcinomas (HNSCCs). Consistent with this, Detroit-562 expressed TLR2, TLR3 and TLR5, whereas NL-20 expressed mainly TLR3 and HNECs expressed TLR2-5. In Detroit-562, Pam(3)CSK(4), poly(I:C) and flagellin, ligands for TLR2, TLR3 and TLR5, respectively, induced an up-regulation of intercellular adhesion molecule 1 (ICAM-1), an increase in interleukin (IL)-6 and IL-8 secretion and a decrease in cell viability. Additionally, poly(I:C) affected IL-1 beta production and the migratory behaviour of Detroit-562. NL-20 responded with a slight increase in IL-8 secretion upon poly(I:C) stimulation. Poly(I:C) induced a small increase in IL-1 beta, IL-6 and IL-8 production in HNECs, while Pam(3)CSK(4) increased viability. The TLR signalling was transcription-dependent, but the pathways involved differed among TLRs as well as cells. In Detroit-562, TLR2 and TLR5 activation was mediated via c-jun N-terminal kinase (JNK)-, p38-, phosphatidylinositol 3-kinase (PI3K)- and nuclear factor (NF)-kappa B-related pathways, while TLR3 was dependent on NF-kappa B. In NL-20, TLR3 signalled via p38, and in HNECs, NF-kappa B, JNK and extracellular signal-regulated kinase (ERK) appeared to be involved. We found that TLR agonists induced a robust response in HNSCCs, characterized by generation of inflammation and cell death. A similar response was not seen in normal epithelial cells. Thus, the TLR system should be considered an important target in future antitumour immunotherapy. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Toll-like, signal transduction, inflammation, apoptosis, cancer, receptors
in
Immunology
volume
128
issue
1
pages
600 - 611
publisher
Wiley-Blackwell
external identifiers
  • wos:000268703800045
  • scopus:68249138311
ISSN
0019-2805
DOI
10.1111/j.1365-2567.2008.03041.x
language
English
LU publication?
yes
id
90bb4c47-d290-45b6-a1b0-70e4863740e3 (old id 1459955)
date added to LUP
2009-08-31 11:03:05
date last changed
2017-05-28 03:42:15
@article{90bb4c47-d290-45b6-a1b0-70e4863740e3,
  abstract     = {P>Toll-like receptors (TLRs) are increasingly implicated in the pathogenesis of cancer. The present study describes TLR expression and function in healthy and malignant airway epithelial cells. The squamous cell carcinoma cell line Detroit-562 was compared with the healthy bronchial epithelial cell line NL-20 and primary human nasal epithelial cells (HNECs). TLR2, TLR3 and TLR5 were present in primary head and neck squamous cell carcinomas (HNSCCs). Consistent with this, Detroit-562 expressed TLR2, TLR3 and TLR5, whereas NL-20 expressed mainly TLR3 and HNECs expressed TLR2-5. In Detroit-562, Pam(3)CSK(4), poly(I:C) and flagellin, ligands for TLR2, TLR3 and TLR5, respectively, induced an up-regulation of intercellular adhesion molecule 1 (ICAM-1), an increase in interleukin (IL)-6 and IL-8 secretion and a decrease in cell viability. Additionally, poly(I:C) affected IL-1 beta production and the migratory behaviour of Detroit-562. NL-20 responded with a slight increase in IL-8 secretion upon poly(I:C) stimulation. Poly(I:C) induced a small increase in IL-1 beta, IL-6 and IL-8 production in HNECs, while Pam(3)CSK(4) increased viability. The TLR signalling was transcription-dependent, but the pathways involved differed among TLRs as well as cells. In Detroit-562, TLR2 and TLR5 activation was mediated via c-jun N-terminal kinase (JNK)-, p38-, phosphatidylinositol 3-kinase (PI3K)- and nuclear factor (NF)-kappa B-related pathways, while TLR3 was dependent on NF-kappa B. In NL-20, TLR3 signalled via p38, and in HNECs, NF-kappa B, JNK and extracellular signal-regulated kinase (ERK) appeared to be involved. We found that TLR agonists induced a robust response in HNSCCs, characterized by generation of inflammation and cell death. A similar response was not seen in normal epithelial cells. Thus, the TLR system should be considered an important target in future antitumour immunotherapy.},
  author       = {Rydberg, Camilla and Månsson, Anne and Uddman, Rolf and Riesbeck, Kristian and Cardell, Lars-Olaf},
  issn         = {0019-2805},
  keyword      = {Toll-like,signal transduction,inflammation,apoptosis,cancer,receptors},
  language     = {eng},
  number       = {1},
  pages        = {600--611},
  publisher    = {Wiley-Blackwell},
  series       = {Immunology},
  title        = {Toll-like receptor agonists induce inflammation and cell death in a model of head and neck squamous cell carcinomas},
  url          = {http://dx.doi.org/10.1111/j.1365-2567.2008.03041.x},
  volume       = {128},
  year         = {2009},
}