Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
J Clin Invest. 2021 Mar 15;131(6). doi: 10.1172/JCI143763.
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.
大气臭氧的持续变薄会使地球免受有害紫外线 (UVR) 的伤害，这将导致更多的 UVR 到达地球表面，从而使皮肤癌的发病率急剧上升。除了促进皮肤细胞癌变外，UVR 还是导致皮肤“光老化”的主要外在驱动力，这种光老化是与年龄相关的皮肤变化。我们目前正处于了解内在老化在黑色素瘤中的作用的初步阶段，而光老化对皮肤微环境的肿瘤促进作用在很大程度上仍未得到探索。在这篇综述中，我们概述了 UVR 对皮肤微环境的影响，讨论了与内在老化观察到的变化趋同或趋异的变化。内在和外在老化会促使皮肤细胞群发生表型变化，改变黑色素生成、细胞外基质沉积、炎症和免疫反应等基本过程。鉴于这些过程与癌症的相关性，我们讨论了光老化如何使皮肤微环境有利于黑色素瘤的进展。
