The dark side of daylight: photoaging and the tumor microenvironment in melanoma progression

J Clin Invest. 2021 Mar 15;131(6):e143763. doi: 10.1172/JCI143763.

Abstract

Continued thinning of the atmospheric ozone, which protects the earth from damaging ultraviolet radiation (UVR), will result in elevated levels of UVR reaching the earth's surface, leading to a drastic increase in the incidence of skin cancer. In addition to promoting carcinogenesis in skin cells, UVR is a potent extrinsic driver of age-related changes in the skin known as "photoaging." We are in the preliminary stages of understanding of the role of intrinsic aging in melanoma, and the tumor-permissive effects of photoaging on the skin microenvironment remain largely unexplored. In this Review, we provide an overview of the impact of UVR on the skin microenvironment, addressing changes that converge or diverge with those observed in intrinsic aging. Intrinsic and extrinsic aging promote phenotypic changes to skin cell populations that alter fundamental processes such as melanogenesis, extracellular matrix deposition, inflammation, and immune response. Given the relevance of these processes in cancer, we discuss how photoaging might render the skin microenvironment permissive to melanoma progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / immunology
  • Aging / metabolism
  • Aging / pathology
  • Animals
  • Disease Progression
  • Extracellular Matrix / radiation effects
  • Humans
  • Immune Tolerance / radiation effects
  • Melanins / biosynthesis
  • Melanoma / etiology*
  • Melanoma / immunology
  • Melanoma / metabolism
  • Mice
  • Receptors, Aryl Hydrocarbon / metabolism
  • Skin / immunology
  • Skin / metabolism
  • Skin / radiation effects
  • Skin Aging / radiation effects*
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism
  • Tumor Microenvironment / radiation effects*
  • Ultraviolet Rays / adverse effects
  • Urocanic Acid / metabolism
  • Vitamin D / metabolism

Substances

  • Melanins
  • Receptors, Aryl Hydrocarbon
  • Vitamin D
  • Urocanic Acid