Universität zu Köln

Uzun, Senem, Korkmaz, Yueksel, Wuerdemann, Nora ORCID: 0000-0002-1092-689X, Arolt, Christoph, Puladi, Behrus ORCID: 0000-0001-5909-6105, Siefer, Oliver G., Doenmez, Hanife G., Hufbauer, Martin ORCID: 0000-0003-4106-0520, Akguel, Baki, Klussmann, Jens P. and Huebbers, Christian U. (2021). Comprehensive Analysis of VEGFR2 Expression in HPV-Positive and -Negative OPSCC Reveals Differing VEGFR2 Expression Patterns. Cancers, 13 (20). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary:& nbsp;Up to 50% of oropharyngeal squamous cell carcinomas (OPSCC) are associated with human papillomavirus type 16 (HPV16), the annual incidence of which is steadily increasing. HPV-positive and -negative OPSCC exhibit a different biology, which is characterized by distinct mutation signatures and expression patterns. It is known that VEGFR2 is commonly overexpressed in HNSCC, but the influence of HPV on VEGFR2 in OPSCC is still unknown, although VEGFR2 has emerged as a promising target in tumor therapy. The aim of our study was to evaluate whether HPV exerts specific effects on VEGFR2 expression in OPSCC and thus possibly on the regulation of vascularization. Interestingly, while HPV-negative carcinoma upregulates VEGFR2 in tumor cells, in HPV-positive carcinoma VEGFR2 is upregulated in tumor-supporting blood vessels. HPV-positive OPSCC with high VEGFR2 expression is associated with poor prognosis, supporting the prognostic significance of deregulated VEGF signaling for OPSCC patients.</p> <br></p> VEGF signaling regulated by the vascular endothelial growth factor receptor 2 (VEGFR2) plays a decisive role in tumor angiogenesis, initiation and progression in several tumors including HNSCC. However, the impact of HPV-status on the expression of VEGFR2 in OPSCC has not yet been investigated, although HPV oncoproteins E6 and E7 induce VEGF-expression. In a series of 56 OPSCC with known HPV-status, VEGFR2 expression patterns were analyzed both in blood vessels from tumor-free and tumor-containing regions and within tumor cells by immunohistochemistry using densitometry. Differences in subcellular colocalization of VEGFR2 with endothelial, tumor and stem cell markers were determined by double-immunofluorescence imaging. Immunohistochemical results were correlated with clinicopathological data. HPV-infection induces significant downregulation of VEGFR2 in cancer cells compared to HPV-negative tumor cells (p = 0.012). However, with respect to blood vessel supply, the intensity of VEGFR2 staining differed only in HPV-positive OPSCC and was upregulated in the blood vessels of tumor-containing regions (p < 0.0001). These results may suggest different routes of VEGFR2 signaling depending on the HPV-status of the OPSCC. While in HPV-positive OPSCC, VEGFR2 might be associated with increased angiogenesis, in HPV-negative tumors, an autocrine loop might regulate tumor cell survival and invasion.</p>

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Uzun, Senem UNSPECIFIED UNSPECIFIED UNSPECIFIED Korkmaz, Yueksel UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuerdemann, Nora UNSPECIFIED orcid.org/0000-0002-1092-689X UNSPECIFIED Arolt, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Puladi, Behrus UNSPECIFIED orcid.org/0000-0001-5909-6105 UNSPECIFIED Siefer, Oliver G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Doenmez, Hanife G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hufbauer, Martin UNSPECIFIED orcid.org/0000-0003-4106-0520 UNSPECIFIED Akguel, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED Klussmann, Jens P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huebbers, Christian U. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-590098
DOI:	10.3390/cancers13205221
Journal or Publication Title:	Cancers
Volume:	13
Number:	20
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; CANCER STEM-CELLS; HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CANCER; HEAD; ANGIOGENESIS; PHOSPHORYLATION; KERATINOCYTES; MECHANISMS; RECEPTORS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59009