Universität zu Köln

Hufbauer, Martin, Maltseva, Margaret, Meinrath, Jeannine, Lechner, Axel, Beutner, Dirk, Huebbers, Christian U. and Akguel, Baki (2018). HPV16 increases the number of migratory cancer stem cells and modulates their miRNA expression profile in oropharyngeal cancer. Int. J. Cancer, 143 (6). S. 1426 - 1440. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

Human papillomavirus type 16 (HPV16) is a major risk for development of oropharyngeal squamous-cell-carcinoma (OPSCC). Although HPV+ OPSCC metastasize faster than HPV- tumors, they have a better prognosis. The molecular and cellular alterations underlying this pathobiology of HPV+ OPSCC remain elusive. In this study, we examined whether expression of HPV16-E6E7 targets the number of migratory and stationary cancer stem cells (CSC). Furthermore, we wanted to elucidate if aberrantly expressed miRNAs in migratory CSC may be responsible for progression of OPSCCs and whether they may serve as potential novel biomarkers for increased potential of metastasis. Our studies revealed that HPV16-E6E7 expression leads to an increase in the number of stationary (CD44(high)/EpCAM(high)) stem cells in primary keratinocyte cultures. Most importantly, expression of E6E7 in the cell line H357 increased the migratory (CD44(high)/EpCAM(low)) CSC pool. This increase in migratory CSCs could also be confirmed in HPV+ OPSCC. Differentially expressed miRNAs from HPV16-E6E7 positive CD44(high)/EpCAM(low) CSCs were validated by RT-qPCR and in situ hybridization on HPV16 1 OPSCCs. These experiments led to the identification of miR-3194-5p, which is upregulated in primary HPV16(+) OPSCC and matched metastasis. MiR-1281 was also found to be highly expressed in HPV+ and HPV- metastasis. As inhibition of this miRNA led to a markedly reduction of CD44(high)/EpCAM(low) cells, it may prove to be a promising drug target. Taken together, our findings highlight the capability of HPV16 to modify the phenotype of infected stem cells and that miR-1281 and miR3194-5p may represent promising targets to block metastatic spread of OPSCC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hufbauer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Maltseva, Margaret UNSPECIFIED UNSPECIFIED UNSPECIFIED Meinrath, Jeannine UNSPECIFIED UNSPECIFIED UNSPECIFIED Lechner, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Beutner, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Huebbers, Christian U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Akguel, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-172886
DOI:	10.1002/ijc.31538
Journal or Publication Title:	Int. J. Cancer
Volume:	143
Number:	6
Page Range:	S. 1426 - 1440
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN-PAPILLOMAVIRUS; MICRORNA EXPRESSION; GENE-EXPRESSION; NECK-CANCER; DECREASED EXPRESSION; HEAD; CARCINOMA; LINES; IDENTIFICATION; DNA Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17288