Universität zu Köln

Hufbauer, Martin, Biddle, Adrian ORCID: 0000-0003-4371-9720, Borgogna, Cinzia ORCID: 0000-0001-9973-2620, Gariglio, Marisa ORCID: 0000-0002-5187-0140, Doorbar, John, Storey, Alan ORCID: 0000-0003-2001-9772, Pfister, Herbert, Mackenzie, Ian and Akguel, Baki (2013). Expression of Betapapillomavirus Oncogenes Increases the Number of Keratinocytes with Stem Cell-Like Properties. J. Virol., 87 (22). S. 12158 - 12166. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5514

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Abstract

Human papillomaviruses (HPV) of genus Betapapillomavirus (betaPV) are associated with nonmelanoma skin cancer development in epidermodysplasia verruciformis (EV) and immunosuppressed patients. Epidemiological and molecular studies suggest a carcinogenic activity of betaPV during early stages of cancer development. Since viral oncoproteins delay and perturb keratinocyte differentiation, they may have the capacity to either retain or confer a stem cell-like state on oncogene-expressing cells. The aim of this study was to determine (i) whether betaPV alters the expression of cell surface markers, such as CD44 and epithelial cell adhesion molecule (EpCAM), that have been associated with epithelial stemness, and (ii) whether this confers functional stem cell-like properties to human cutaneous keratinocytes. Fluorescence-activated cell sorter (FACS) analysis revealed an increase in the number of cells with high CD44 and EpCAM expression in keratinocyte cultures expressing HPV type 8 (HPV8) oncogenes E2, E6, and E7. Particularly through E7 expression, a distinct increase in clonogenicity and in the formation and size of tumor spheres was observed, accompanied by reduction of the epithelial differentiation marker Calgranulin B. These stem cell-like properties could be attributed to the pool of CD44(high) EpCAM(high) cells, which was increased within the E7 cultures of HPV5, -8, and -20. Enhanced EpCAM levels were present in organotypic skin cultures of primary keratinocytes expressing E7 of the oncogenic HPV types HPV5, -8, and -16 and in clinical samples from EV patients. In conclusion, our data show that betaPV may increase the number of stem cell-like cells present during early carcinogenesis and thus enable the persistence and accumulation of DNA damage necessary to generate malignant stem cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hufbauer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Biddle, Adrian UNSPECIFIED orcid.org/0000-0003-4371-9720 UNSPECIFIED Borgogna, Cinzia UNSPECIFIED orcid.org/0000-0001-9973-2620 UNSPECIFIED Gariglio, Marisa UNSPECIFIED orcid.org/0000-0002-5187-0140 UNSPECIFIED Doorbar, John UNSPECIFIED UNSPECIFIED UNSPECIFIED Storey, Alan UNSPECIFIED orcid.org/0000-0003-2001-9772 UNSPECIFIED Pfister, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Mackenzie, Ian UNSPECIFIED UNSPECIFIED UNSPECIFIED Akguel, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-473531
DOI:	10.1128/JVI.01510-13
Journal or Publication Title:	J. Virol.
Volume:	87
Number:	22
Page Range:	S. 12158 - 12166
Date:	2013
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5514
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPIDERMODYSPLASIA-VERRUCIFORMIS PATIENTS; HUMAN-PAPILLOMAVIRUS-DNA; BREAST-CANCER; ADHESION MOLECULE; MYELOID-LEUKEMIA; UP-REGULATION; SKIN-CANCER; IDENTIFICATION; TUMORS; EPCAM Multiple languages Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47353