Reference SummaryHuth S, Sci Rep 2023 Jul 18;13(1):11611

Title

 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.

Authors

 Huth S; Huth L; Heise R; Marquardt Y; Lopopolo L; Piecychna M; Boor P; Fingerle-Rowson G; Kapurniotu A; Yazdi AS; Bucala R; Bernhagen J; Baron JM

Journal

 Sci Rep

Volume

 13

Issue

 1

Year

 2023

Pages

 11611

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.

Links

 J:338199 – MGI References
37464010 – National Library of Medicine/PubMed

Strain Notes

Strain Note
Crl:SKH1-Hrhr "All mice were outbred to the SKH-1 background (Crl:SKH1-Hrhr; Charles River, Sulzfeld, Germany) for 10 generations."
Hairless mutation control cohort, wild type for both KO alleles in this study.
Crl:SKH1-Hrhr Ddttm1.1Lhy "All mice were outbred to the SKH-1 background (Crl:SKH1-Hrhr; Charles River, Sulzfeld, Germany) for 10 generations."
Crl:SKH1-Hrhr Ddttm1.1Lhy Miftm1Gfr "All mice were outbred to the SKH-1 background (Crl:SKH1-Hrhr; Charles River, Sulzfeld, Germany) for 10 generations."
Crl:SKH1-Hrhr Miftm1Gfr "All mice were outbred to the SKH-1 background (Crl:SKH1-Hrhr; Charles River, Sulzfeld, Germany) for 10 generations."

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
Crl:SKH1-Hrhr Skin cyst
  • ultraviolet-B radiation (UVB)
 Skin

0
Crl:SKH1-Hrhr Miftm1Gfr Skin cyst
  • ultraviolet radiation (UV)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Skin cyst
  • ultraviolet radiation (UV)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Miftm1Gfr Skin cyst
  • ultraviolet radiation (UV)
 Skin

observed
Crl:SKH1-Hrhr Skin papilloma
  • ultraviolet-B radiation (UVB)
 Skin

observed
Crl:SKH1-Hrhr Skin papilloma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

observed
Crl:SKH1-Hrhr Miftm1Gfr Skin papilloma
  • ultraviolet radiation (UV)
 Skin

observed
Crl:SKH1-Hrhr Miftm1Gfr Skin papilloma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Skin papilloma
  • ultraviolet radiation (UV)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Skin papilloma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Miftm1Gfr Skin papilloma
  • ultraviolet radiation (UV)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Miftm1Gfr Skin papilloma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

observed
Crl:SKH1-Hrhr Skin squamous cell carcinoma
  • ultraviolet-B radiation (UVB)
 Skin

observed
Crl:SKH1-Hrhr Skin squamous cell carcinoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

observed
Crl:SKH1-Hrhr Miftm1Gfr Skin squamous cell carcinoma
  • ultraviolet radiation (UV)
 Skin

observed
Crl:SKH1-Hrhr Miftm1Gfr Skin squamous cell carcinoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Skin squamous cell carcinoma
  • ultraviolet radiation (UV)
 Skin

0
Crl:SKH1-Hrhr Ddttm1.1Lhy Skin squamous cell carcinoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Miftm1Gfr Skin squamous cell carcinoma
  • ultraviolet radiation (UV)
 Skin

observed
Crl:SKH1-Hrhr Ddttm1.1Lhy Miftm1Gfr Skin squamous cell carcinoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

observed
Crl:SKH1-Hrhr Skin tumor
  • ultraviolet-B radiation (UVB)
 Skin

100
Crl:SKH1-Hrhr Skin tumor
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

100
Crl:SKH1-Hrhr Miftm1Gfr Skin tumor
  • ultraviolet radiation (UV)
 Skin

25 - 35
Crl:SKH1-Hrhr Miftm1Gfr Skin tumor
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

100
Crl:SKH1-Hrhr Ddttm1.1Lhy Skin tumor
  • ultraviolet radiation (UV)
 Skin

91 - 92
Crl:SKH1-Hrhr Ddttm1.1Lhy Skin tumor
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

100
Crl:SKH1-Hrhr Ddttm1.1Lhy Miftm1Gfr Skin tumor
  • ultraviolet radiation (UV)
 Skin

42 - 45
Crl:SKH1-Hrhr Ddttm1.1Lhy Miftm1Gfr Skin tumor
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Skin

100