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

Sebastian Huth, Laura Huth, Ruth Heise, Yvonne Marquardt, Linda Lopopolo, Marta Piecychna, Peter Boor, Günter Fingerle-Rowson, Aphrodite Kapurniotu, Amir S. Yazdi, Richard Bucala, Jürgen Bernhagen, Jens Malte Baron

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Non-melanoma skin cancer (NMSC) is the most common cancer in Caucasians worldwide. We investigated the pathophysiological role of MIF and its homolog D-DT in UVB- and chemically induced NMSC using Mif −/−, D-dt −/− and Mif −/− /D-dt −/− mice on a hairless SKH1 background. Knockout of both cytokines showed similar attenuating effects on inflammation after acute UVB irradiation and tumor formation during chronic UVB irradiation, without additive protective effects noted in double knockout mice, indicating that both cytokines activate a similar signaling threshold. In contrast, genetic deletion of Mif and D-dt had no major effects on chemically induced skin tumors. To get insight into the contributing mechanisms, we used an in vitro 3D skin model with incorporated macrophages. Application of recombinant MIF and D-DT led to an accumulation of macrophages within the epidermal part that could be reversed by selective inhibitors of MIF and D-DT pathways. In summary, our data indicate that MIF and D-DT contribute to the development and progression of UVB- but not chemically induced NMSC, a role at least partially accounted by effects of both cytokines on epidermal macrophage accumulation. These data highlight that MIF and D-DT are both potential therapeutic targets for the prevention of photocarcinogenesis but not chemical carcinogenesis.

Original languageEnglish
Article number11611
JournalScientific Reports
Volume13
Issue number1
DOIs
StatePublished - Dec 2023

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this