Non-melanoma skin cancer (NMSC) is the most common cancer in Caucasians worldwide, caused by chronic exposure to environmental factors such as ultraviolet (UV) radiation and chemicals. MIF is a pleiotropic cytokine that is described as a pro-tumorigenic factor in various tumour entities. D-DT was recently described as a homolog of MIF that shares many biological activities. The aim of the present study was to assess the pathophysiological role of MIF and D-DT in the development and progression of UVB and chemically induced NMSC. Investigating the effects of MIF and D-DT during the acute inflammatory phase, we irradiated WT, Mif-/-, D-dt-/- and Mif-/-/D-dt-/- SKH1-HrHr mice dorsally with a single UVB dose of 2240 J/m2. Here we found that the epidermal thickness was significantly increased in UVB-irradiated Mif-/- and D-dt-/- mice compared to WT controls. For long-term UVB irradiation studies mice were irradiated three times a week for 25 weeks. Mif-/-, D-dt-/- and Mif-/-/D-dt-/- mice developed significantly later and fewer tumors. For chemical skin carcinogenesis, mice were treated with benzo(α)pyrene twice a week for 23 weeks. In contrast to our long-term UVB experiments, we did not observe any differences in the timing of tumor onset and tumor incidence between all groups. These data indicate that MIF and D-DT play important roles in the development and progression of UVB, but not chemically induced NMSC.

ESDR259 - Macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (D-DT) are significant promotors of UVB, but not chemically induced non-melanoma skin cancer

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING