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The dark side of daylight: photoaging and the tumor microenvironment in melanoma progression
Asurayya Worrede, … , Stephen M. Douglass, Ashani T. Weeraratna
Asurayya Worrede, … , Stephen M. Douglass, Ashani T. Weeraratna
Published March 15, 2021
Citation Information: J Clin Invest. 2021;131(6):e143763. https://doi.org/10.1172/JCI143763.
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Review Series

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

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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.

Authors

Asurayya Worrede, Stephen M. Douglass, Ashani T. Weeraratna

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Figure 3

Differences between the chronologically aged and photoaged skin microenvironments.

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Differences between the chronologically aged and photoaged skin microenv...
A summary of key differences between chronologically aged (A) and photoaged (B) skin as described in “The photoaged microenvironment and melanoma progression.” Intrinsic aging is associated with decreases in melanocyte proliferation and melanogenesis, resulting in hypopigmentation of the epidermis. In contrast, UVR-exposed keratinocytes induce melanogenesis, thereby causing regions of hyperpigmentation clinically recognized as “sun spots.” Both the intrinsically aged and the photoaged fibroblasts of the dermal skin layer express SASP and increased production of MMPs, which leads to collagen breakdown and ECM remodeling. The mechanisms driving spontaneous collagen fragmentation in intrinsically aged skin remain largely unknown. However, in photoaged fibroblasts, this process is thought to be mediated by an increased hyaluronic acid depolymerization by HYBID and downregulation of collagen production by altered miRNAs and circRNAs.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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