Change search
ReferencesLink to record
Permanent link

Direct link
S100A9 Interaction with TLR4 Promotes Tumor Growth
Show others and affiliations
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 3, e34207- p.Article in journal (Refereed) Published
Abstract [en]

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 TGF beta 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.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science , 2012. Vol. 7, no 3, e34207- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-56702DOI: 10.1371/journal.pone.0034207ISI: 000304489000074OAI: diva2:537400
Available from: 2012-06-26 Created: 2012-06-25 Last updated: 2012-06-26Bibliographically approved

Open Access in DiVA

fulltext(728 kB)87 downloads
File information
File name FULLTEXT02.pdfFile size 728 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Wikström, PernillaBergh, Anders
By organisation
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 87 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 97 hits
ReferencesLink to record
Permanent link

Direct link