S100A9 Interaction with TLR4 Promotes Tumor Growth.
Källberg, Eva LU ; Vogl, Thomas ; Liberg, David ; Olsson, Anders ; Björkman, Per LU
; Wikström, Pernilla
; Bergh, Anders
; Roth, Johannes
; Ivars, Fredrik
LU
and Leanderson, Tomas
LU
(2012)
In PLoS ONE
7(3).
- Abstract
- By breeding TRAMP mice with S100A9 knock-out (S100A9(-/-)) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+) S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+) macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/-) and TLR4(-/-), but not in RAGE(-/-) animals lacking an alternative S100A9 receptor. When expression of immune-regulating... (More)
- By breeding TRAMP mice with S100A9 knock-out (S100A9(-/-)) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+) S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+) macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/-) and TLR4(-/-), but not in RAGE(-/-) animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFβ expression in splenic CD11b(+) cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2519907
- author
- Källberg, Eva
LU
; Vogl, Thomas
; Liberg, David
; Olsson, Anders
; Björkman, Per
LU
; Wikström, Pernilla
; Bergh, Anders
; Roth, Johannes
; Ivars, Fredrik
LU
and Leanderson, Tomas
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 7
- issue
- 3
- article number
- e34207
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000304489000074
- pmid:22470535
- scopus:84859044056
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0034207
- language
- English
- LU publication?
- yes
- id
- 2ad4f386-0eff-435d-9f8c-4e2a16a9de59 (old id 2519907)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22470535?dopt=Abstract
- date added to LUP
- 2016-04-01 15:03:52
- date last changed
- 2022-04-22 06:36:46
@article{2ad4f386-0eff-435d-9f8c-4e2a16a9de59,
abstract = {{By breeding TRAMP mice with S100A9 knock-out (S100A9(-/-)) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+) S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+) macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/-) and TLR4(-/-), but not in RAGE(-/-) animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFβ expression in splenic CD11b(+) cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies.}},
author = {{Källberg, Eva and Vogl, Thomas and Liberg, David and Olsson, Anders and Björkman, Per and Wikström, Pernilla and Bergh, Anders and Roth, Johannes and Ivars, Fredrik and Leanderson, Tomas}},
issn = {{1932-6203}},
language = {{eng}},
number = {{3}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{S100A9 Interaction with TLR4 Promotes Tumor Growth.}},
url = {{https://lup.lub.lu.se/search/files/4321728/2535643.pdf}},
doi = {{10.1371/journal.pone.0034207}},
volume = {{7}},
year = {{2012}},
}