| First Author | Gebhardt C | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 2 | Pages | 275-85 |
| PubMed ID | 18208974 | Mgi Jnum | J:134050 |
| Mgi Id | MGI:3784901 | Doi | 10.1084/jem.20070679 |
| Citation | Gebhardt C, et al. (2008) RAGE signaling sustains inflammation and promotes tumor development. J Exp Med 205(2):275-85 |
| abstractText | A broad range of experimental and clinical evidence has highlighted the central role of chronic inflammation in promoting tumor development. However, the molecular mechanisms converting a transient inflammatory tissue reaction into a tumor-promoting microenvironment remain largely elusive. We show that mice deficient for the receptor for advanced glycation end-products (RAGE) are resistant to DMBA/TPA-induced skin carcinogenesis and exhibit a severe defect in sustaining inflammation during the promotion phase. Accordingly, RAGE is required for TPA-induced up-regulation of proinflammatory mediators, maintenance of immune cell infiltration, and epidermal hyperplasia. RAGE-dependent up-regulation of its potential ligands S100a8 and S100a9 supports the existence of an S100/RAGE-driven feed-forward loop in chronic inflammation and tumor promotion. Finally, bone marrow chimera experiments revealed that RAGE expression on immune cells, but not keratinocytes or endothelial cells, is essential for TPA-induced dermal infiltration and epidermal hyperplasia. We show that RAGE signaling drives the strength and maintenance of an inflammatory reaction during tumor promotion and provide direct genetic evidence for a novel role for RAGE in linking chronic inflammation and cancer. |
