1. Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors
- Author
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Edwige Roy, Ho Yi Wong, Rehan Villani, Thomas Rouille, Basit Salik, Seen Ling Sim, Valentine Murigneux, Mitchell S. Stark, J. Lynn Fink, H. Peter Soyer, Graeme Walker, J. Guy Lyons, Nicholas Saunders, and Kiarash Khosrotehrani
- Subjects
multicolor lineage tracing ,basal cell carcinoma ,non-melanoma skin cancer ,ultra-violet radiation ,hair follicles ,field carcinogenesis ,Biology (General) ,QH301-705.5 - Abstract
Summary: To better understand the influence of ultraviolet (UV) irradiation on the initial steps of skin carcinogenesis, we examine patches of labeled keratinocytes as a proxy for clones in the interfollicular epidermis (IFE) and measure their size variation upon UVB irradiation. Multicolor lineage tracing reveals that in chronically irradiated skin, patches near hair follicles (HFs) increase in size, whereas those far from follicles do not change. This is explained by proliferation of basal epidermal cells within 60 μm of HF openings. Upon interruption of UVB, patch size near HFs regresses significantly. These anatomical differences in proliferative behavior have significant consequences for the cell of origin of basal cell carcinomas (BCCs). Indeed, a UV-inducible murine BCC model shows that BCC patches are more frequent, larger, and more invasive near HFs. These findings have major implications for the prevention of field cancerization in the epidermis.
- Published
- 2020
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