Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors.
Animals
Carcinoma, Basal Cell
/ metabolism
Cell Proliferation
Cyclin D1
/ metabolism
Disease Models, Animal
Epidermis
/ metabolism
Hair Follicle
/ pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasms, Radiation-Induced
/ metabolism
Skin Neoplasms
/ metabolism
Stem Cells
/ cytology
Tumor Suppressor Protein p53
/ genetics
Ultraviolet Rays
basal cell carcinoma
field carcinogenesis
hair follicles
multicolor lineage tracing
mutation burden
non-melanoma skin cancer
photodamaged skin
ultra-violet radiation
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
02 06 2020
02 06 2020
Historique:
received:
30
10
2019
revised:
12
03
2020
accepted:
06
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
4
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32492418
pii: S2211-1247(20)30672-0
doi: 10.1016/j.celrep.2020.107702
pii:
doi:
Substances chimiques
Tumor Suppressor Protein p53
0
Cyclin D1
136601-57-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107702Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.