Abstract
Lgr6+ cells have been identified as a novel class of proliferating (Ki67+) stem cells in mouse epidermis. We investigated their response to UV exposure in Lgr6-EGFP-Ires-CreERT2/R26R-LacZ haired and hairless mice and whether they become initiating cells of UV- or chemically induced skin tumors. UV overexposure erased Lgr6+ cells (EGFP+) from the interfollicular epidermis (IFE), but - as after wounding - they apparently repopulated the IFE from the hair follicles. Under sub-sunburn chronic UV exposure, Lgr6+ cells and their progeny (LacZ+ after pulse of tamoxifen) diminished strongly in the IFE. Although the inter-tumoral IFE clearly showed Lgr6 progeny, none of the UV- or chemically induced tumors (n = 22 and 41, respectively) appeared to be clonal expansions of Lgr6+ stem cells; i.e. no Lgr6+ cells or progeny in the proliferating tumor bulk. In checking for promoter methylation we found it to occur stochastically for the EGFP-Cre cassette. Lgr6 mRNA measured by qPCR was found to be diminished in skin tumors (also in UV tumors from wt type mice). The ratio of Lgr6/Ki67 was significantly reduced, pointing at a loss of Lgr6+ cells from the proliferative pool. Our data show that Lgr6+ cells are not major tumor-initiating cells in skin carcinogenesis.
Highlights
Skin cancer is the most common cancer in whiteskinned European ancestral populations; the incidence of non-melanoma and melanoma skin cancer is rising [1, 2]
We first ascertained whether Lgr6+ stem cells were present in the epidermis of hairless mice
We stained for Lgr6+ stem cells, using an anti-EGFP antibody, in skin samples taken at different time points after UV overexposure; see Figures 2 and 3(E-H) for hairless and haired mice, respectively
Summary
Skin cancer is the most common cancer in whiteskinned European ancestral populations; the incidence of non-melanoma (squamous cell carcinoma and basal cell carcinoma) and melanoma skin cancer is rising [1, 2]. UV exposure plays an important role in the etiology of these skin cancers [3, 4]. Cancer is a multistep process (multiple ‘hits’ or mutations) that eventually results in a malignant cell sprouting into a cancerous growth [5]. Since stem cells are long residing cells, these cells are prime candidates to accumulate oncogenic changes over time. One of the more recently identified stem cell populations in the skin is that of Lgr6+ cells [6]. We posed the question whether these stem cells are targeted in experimental skin carcinogenesis by exogenic agents
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
