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

Lanfredini, Simone
Olivero, Carlotta
Borgogna, Cinzia
Calati, Federica
Powell, Kathryn
Davies, Kelli-Jo
De Andrea, Marco
Harries, Sarah
Tang, Hiu
Pfister, Herbert
Gariglio, Marisa
Patel, Girish K

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Publication date

October 2017

DOI

10.1016/j.jid.2017.04.039

Publisher

Elsevier BV

Abstract

-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+ kera...