Universität zu Köln

Ding, Xiaolei, Lucas, Tina, Marcuzzi, Gian P., Pfister, Herbert and Eming, Sabine A. (2015). Distinct Functions of Epidermal and Myeloid-Derived VEGF-A in Skin Tumorigenesis Mediated by HPV8. Cancer Res., 75 (2). S. 330 - 344. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1538-7445

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Abstract

Beta human papillomaviruses (HPV) have been suspected to be carcinogenic in nonmelanoma skin cancers (NMSC), but the basis for potential viral contributions to these cancers is poorly understood. In particular, it is unresolved how HPV-infected keratinocytes escape cell-cycle control and whether their cross-talk with immune cells is critical for tumorigenesis. In nonviral preclinical models, the angiogenic cytokine VEGF-A has been identified as a critical regulator of NMSC. In this study, we dissected the contribution of epidermal versus myeloid cell-derived VEGF-A in HPV-mediated skin cancer by interbreeding an HPV8 transgenic mouse model with a conditional disruption of VEGF-A restricted to either epidermal or myeloid cells. Although only epidermal-derived VEGF-A was essential for initiation of skin tumor development, both spontaneously and UV-light triggered, both epidermal and myeloid cell-derived VEGF-A contributed to regeneration-induced tumorigenesis upon HPV8 overexpression, partly not only through a paracrine effect on endothelial cells, but also most probably through an additional autocrine effect on epidermal cells. Our findings offer new mechanistic insights into distinct functions of epidermal versus myeloid cell-derived VEGF-A during HPV-mediated tumorigenesis, with possible implications for preventing this disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ding, Xiaolei UNSPECIFIED UNSPECIFIED UNSPECIFIED Lucas, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Marcuzzi, Gian P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-414612
DOI:	10.1158/0008-5472.CAN-13-3007
Journal or Publication Title:	Cancer Res.
Volume:	75
Number:	2
Page Range:	S. 330 - 344
Date:	2015
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1538-7445
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL-GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS TYPE-8; HUMAN KERATINOCYTES; TRANSGENIC MICE; E6 PROTEINS; EPIDERMODYSPLASIA-VERRUCIFORMIS; TUMOR PROGRESSION; CARCINOGENESIS; ANGIOGENESIS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41461