S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway
2008 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 83, no 6, 1484-1492 p.Article in journal (Refereed) Published
The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity against various cells, especially tumor cells. Here, we present evidence that S100A8/A9 also has cell growth-promoting activity at low concentrations. Receptor of advanced glycation end product (RAGE) gene silencing and cotreatment with a RAGE-specific blocking antibody revealed that this activity was mediated via RAGE ligation. To investigate the signaling pathways, MAPK phosphorylation and NF-κB activation were characterized in S100A8/A9-treated cells. S100A8/A9 caused a significant increase in p38 MAPK and p44/42 kinase phosphorylation, and the status of stress-activated protein kinase/JNK phosphorylation remained unchanged. Treatment of cells with S100A8/A9 also enhanced NF-κB activation. RAGE small interfering RNA pretreatment abrogated the S100A8/A9-induced NF-κB activation. Our data indicate that S100A8/A9-promoted cell growth occurs through RAGE signaling and activation of NF-κB.
Place, publisher, year, edition, pages
eration of American Societies for Experimental Biology , 2008. Vol. 83, no 6, 1484-1492 p.
NF-κB proliferation MRP8 MRP14 endokines S100/calgranulins cytotoxic peptides
Cancer and Oncology Cell Biology Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-86927DOI: 10.1189/jlb.0607397ISI: 000258019800022PubMedID: 18339893OAI: oai:DiVA.org:liu-86927DiVA: diva2:583307