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HPV8 field cancerization in a transgenic mouse model is due to Lrig1+Keratinocyte stem cell expansion

Lanfredini, Simone ORCID:, Olivero, Carlotta ORCID:, Borgogna, Cinzia, Calati, Federica, Powell, Kathryn, Davies, Kelli-Jo, De Andrea, Marco, Harries, Sarah, Tang, Hiu, Pfister, Herbert, Gariglio, Marisa and Patel, Girish K 2017. HPV8 field cancerization in a transgenic mouse model is due to Lrig1+Keratinocyte stem cell expansion. Journal of Investigative Dermatology 137 (10) , pp. 2208-2216. 10.1016/j.jid.2017.04.039

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-HPV cause near ubiquitous latent skin infection within long-lived hair follicle keratinocyte stem cells (HF -HPV viral replication is associated with skin keratosis and cutaneous squamous cell carcinoma (SCC). To determine the role of HF KSC in β-HPV induced skin carcinogenesis, we utilized a transgenic mouse model in which the keratin 14 promoter drives expression of the entire HPV8 early region (HPV8tg). HPV8tg mice developed thicker skin in comparison to wild type littermates consistent with a hyperproliferative epidermis. HF keratinocyte proliferation was evident within the Lrig1+ KSC population (69 vs 55%, p<0.001, n=6), and not in the CD34+, LGR5+ and LGR6+ KSC populations. This was associated with a 2.8-fold expansion in Lrig1+ keratinocytes and 3.8 fold increased colony forming efficiency. Consistent with this, we observed nuclear p63 expression throughout this population and the HF infundibulum and adjoining IFE, associated with a switch from p63 TA isoforms to ΔNp63 isoforms in HPV8tg skin. EV keratosis and in some cases actinic keratoses demonstrated similar histology associated with β-HPV virus reactivation and nuclear p63 expression within the HF infundibulum and perifollicular epidermis. These findings would suggest that β-HPV field cancerization arises from the HF junctional zone and predispose to SCC.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Uncontrolled Keywords: Human Papillomavirus, Field Cancerization, Squamous cell carcinoma, Keratinocyte stem cells
Publisher: Elsevier
ISSN: 0022-202X
Date of First Compliant Deposit: 9 June 2017
Date of Acceptance: 2 May 2017
Last Modified: 07 Jan 2024 03:24

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