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The Role of Classical and Novel Forms of Vitamin D in the Pathogenesis and Progression of Nonmelanoma Skin Cancers

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Sunlight, Vitamin D and Skin Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1268))

Abstract

Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290–400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290–320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body’s requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.

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Acknowledgment

The support of NIH grants 1R01AR073004-01A1 and R01AR071189-01A1 and VA merit grant 1I01BX004293-01A1 to ATS; P01CA210946, R01CA193885, P30 CA013148, and VA grant 101BX003395 to CAE; the National Science Centre of Poland grant 2017/25/B/NZ3/00431 to MAZ; funds for statutory research from Nicolaus Copernicus University to AAB; and the National Health and Medical Research Council of Australia (APP1070688) and Australian Research Council Linkage grant (LP100200680) to RSM are acknowledged. AMJ research was supported by the Intramural Research Program of the NIEHS, NIH (Z01-ES-101585).

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Authors and Affiliations

  1. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA

    Andrzej T. Slominski, Zorica Janjetovic, Tae-Kang Kim, Purushotham Guroji, Craig Elmets & Mohammad Athar

  2. Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, Birmingham, AL, USA

    Andrzej T. Slominski

  3. VA Medical Center, Birmingham, AL, USA

    Andrzej T. Slominski

  4. Department of Human Biology, Institute of Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Toruń, Poland

    Anna A. Brożyna

  5. Department of Histology, Medical University of Gdańsk, Gdańsk, Poland

    Michal A. Zmijewski

  6. Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Radomir M. Slominski

  7. School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia

    Robert C. Tuckey

  8. Physiology & Bosch Institute, School of Medical Sciences, Faculty of Medicine & Health, The University of Sydney, Sydney, NSW, Australia

    Rebecca S. Mason

  9. Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA

    Anton M. Jetten

  10. Center for Clinical and Experimental Photodermatology and Department of Dermatology, Saarland University Medical Center, Homburg, Germany

    Jörg Reichrath

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  1. Andrzej T. Slominski
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    Jörg Reichrath

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Slominski, A.T. et al. (2020). The Role of Classical and Novel Forms of Vitamin D in the Pathogenesis and Progression of Nonmelanoma Skin Cancers. In: Reichrath, J. (eds) Sunlight, Vitamin D and Skin Cancer. Advances in Experimental Medicine and Biology, vol 1268. Springer, Cham. https://doi.org/10.1007/978-3-030-46227-7_13

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