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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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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 1

Similar and diverging features of the hallmarks of aging and cancer.

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Similar and diverging features of the hallmarks of aging and cancer.
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There are many features of the hallmarks of aging, as described in ref. 2 and ref. 197, that can lead to changes in the microenvironment that are permissive of tumor growth. Persistent alterations to intercellular communication and deregulated nutrient signaling that arise with aging can promote proliferative signaling and evasion of growth suppression, both of which are hallmarks of cancer as described in ref. 127. Additional features equivalent between these two processes include genomic instability, deregulated cell energy processes, and chronic inflammation. However, unlike cancer, the aging cell population is also characterized by mechanisms that shorten cellular lifespan, such as stem cell exhaustion, cellular senescence, and telomere attrition. In contrast, cancer cells acquire the ability to constitutively activate prosurvival pathways that resist cell death and allow the transformed cells to avoid immune destruction and to enable replicative immunity. The hallmarks listed in the shaded areas were previously described as unique to aging or cancer.

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

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