Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors
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,
Kiarash Khosrotehrani
Affiliations
Edwige Roy
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Ho Yi Wong
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Rehan Villani
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Thomas Rouille
UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia
Basit Salik
UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia
Seen Ling Sim
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Valentine Murigneux
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Mitchell S. Stark
The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, Brisbane, QLD 4102, Australia
J. Lynn Fink
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
H. Peter Soyer
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia; The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, Brisbane, QLD 4102, Australia
Graeme Walker
QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
J. Guy Lyons
Discipline of Dermatology, Bosch Institute, Charles Perkins Centre, The University of Sydney, NSW 2006, Australia
Nicholas Saunders
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Kiarash Khosrotehrani
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia; UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia; Corresponding author
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.
