原文鏈接：Innate sensing of microbial products promotes wound-induced skin cancer
Esther Hoste, Esther N. Arwert, Rohit Lal, Andrew P. South, Julio C. Salas-Alanis, Dedee F. Murrell, Giacomo Donati & Fiona M. Watt
The association between tissue damage, chronic inflammation and cancer is well known. However, the underlying mechanisms are unclear. Here we characterize a mouse model in which constitutive epidermal extracellular-signal-regulated kinase-MAP-kinase signalling results in epidermal inflammation, and skin wounding induces tumours. We show that tumour incidence correlates with wound size and inflammatory infiltrate. Ablation of ?tumour necrosis factor receptor (TNFR)-1/-2, ?Myeloid Differentiation primary response gene 88 or ?Toll-like receptor (TLR)-5, the bacterial ?flagellin receptor, but not other innate immune sensors, in radiosensitive leukocytes protects against tumour formation. Antibiotic treatment inhibits, wheras injection of ?flagellin induces, tumours in a ?TLR-5-dependent manner. ?TLR-5 is also involved in chemical-induced skin carcinogenesis in wild-type mice. Leukocytic ?TLR-5 signalling mediates upregulation of the alarmin ?HMGB1 (?High Mobility Group Box 1) in wound-induced papillomas. ?HMGB1 is elevated in tumours of patients with Recessive Dystrophic Epidermolysis Bullosa, a disease characterized by chronic skin damage. We conclude that in our experimental model the combination of bacteria, chronic inflammation and wounding cooperate to trigger skin cancer.
