S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway

Open Access
Publisher Website
Google Scholar
Abstract
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.
Funding Information
  • Manitoba Health Research Council
  • CancerCare Manitoba Foundation
  • Interdisciplinary Center for Clinical Research
  • Deutsche Forschungsgemeinschaft
  • U. S. National Institutes of Health (RO1 GM62112, T32 GM08320))
  • Canadian Foundation for Innovation
  • Canada Research Chair
  • Canadian Institutes of Health Research (CIHR)-
  • Manitoba Institute of Child Health
  • German Federal Ministry of Education
  • Science
  • research and technology
  • Landesforschungsschwerpunkt-programm of the Ministry of Science, Research
  • Arts of the Land Baden-Wuerttemberg

This publication has 45 references indexed in Scilit: