Universität zu Köln

Lanfredini, Simone, Olivero, Carlotta ORCID: 0000-0002-8961-6703, Borgogna, Cinzia, Calati, Federica, Powell, Kathryn, Davies, Kelli-Jo, De Andrea, Marco ORCID: 0000-0002-3188-5783, Harries, Sarah, Tang, Hiu Kwan Carolyn, 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. J. Invest. Dermatol., 137 (10). S. 2208 - 2217. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

beta-Human papillomaviruses (HPVs) cause near ubiquitous latent skin infection within long-lived hair follicle (HF) keratinocyte stem cells. In patients with epidermodysplasia verruciformis, beta-HPV viral replication is associated with skin keratosis and cutaneous squamous cell carcinoma. To determine the role of HF keratinocyte stem cells in beta-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 with wild-type littermates consistent with a hyperproliferative epidermis. HF keratinocyte proliferation was evident within the Lrig1 + keratinocyte stem cell population (69 vs. 55%, P < 0.01, n = 7), and not in the CD34+, LGR5+, and LGR6+ keratinocyte stem cell 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 inter-follicular epidermis, associated with a switch from p63 transcriptional activation isoforms to Delta Np63 isoforms in HPV8tg skin. Epidermodysplasia verruciformis keratosis and in some cases actinic keratoses demonstrated similar histology associated with b-HPV reactivation and nuclear p63 expression within the HF infundibulum and perifollicular epidermis. These findings would suggest that b-HPV field cancerization arises from the HF junctional zone and predispose to squamous cell carcinoma.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lanfredini, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Olivero, Carlotta UNSPECIFIED orcid.org/0000-0002-8961-6703 UNSPECIFIED Borgogna, Cinzia UNSPECIFIED UNSPECIFIED UNSPECIFIED Calati, Federica UNSPECIFIED UNSPECIFIED UNSPECIFIED Powell, Kathryn UNSPECIFIED UNSPECIFIED UNSPECIFIED Davies, Kelli-Jo UNSPECIFIED UNSPECIFIED UNSPECIFIED De Andrea, Marco UNSPECIFIED orcid.org/0000-0002-3188-5783 UNSPECIFIED Harries, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Tang, Hiu Kwan Carolyn UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Gariglio, Marisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Patel, Girish K. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-216768
DOI:	10.1016/j.jid.2017.04.039
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	137
Number:	10
Page Range:	S. 2208 - 2217
Date:	2017
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-PAPILLOMAVIRUS INFECTION; SKIN TUMORS; P63; EXPRESSION; PROLIFERATION; PROTEIN; DNA; IMMUNODEFICIENCY; KERATINOCYTES; SUPPRESSOR Multiple languages Dermatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21676