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Authors: Gül, Désirée
Schweitzer, Andrea
Khamis, Aya
Knauer, Shirley K.
Ding, Guo-Bin
Freudelsperger, Laura
Karampinis, Ioannis
Strieth, Sebastian
Hagemann, Jan
Stauber, Roland H.
Title: Impact of secretion-active osteoblast-specific factor 2 in promoting progression and metastasis of head and neck cancer
Online publication date: 13-Jan-2023
Year of first publication: 2022
Language: english
Abstract: Treatment success of head and neck cancer (HNC) is still hampered by tumor relapse due to metastases. Our study aimed to identify biomarkers by exploiting transcriptomics profiles of patient-matched metastases, primary tumors, and normal tissue mucosa as well as the TCGA HNC cohort data sets. Analyses identified osteoblast-specific factor 2 (OSF-2) as significantly overexpressed in lymph node metastases and primary tumors compared to normal tissue. High OSF-2 levels correlate with metastatic disease and reduced overall survival of predominantly HPV-negative HNC patients. No significant correlation was observed with tumor localization or therapy response. These findings were supported by the fact that OSF-2 expression was not elevated in cisplatin-resistant HNC cell lines. OSF-2 was strongly expressed in tumor-associated fibroblasts, suggesting a tumor microenvironment-promoting function. Molecular cloning and expression studies of OSF-2 variants from patients identified an evolutionary conserved bona fide protein secretion signal (1MIPFLPMFSLLLLLIVNPINA21). OSF-2 enhanced cell migration and cellular survival under stress conditions, which could be mimicked by the extracellular administration of recombinant protein. Here, OSF-2 executes its functions via ß1 integrin, resulting in the phosphorylation of PI3K and activation of the Akt/PKB signaling pathway. Collectively, we suggest OSF-2 as a potential prognostic biomarker and drug target, promoting metastases by supporting the tumor microenvironment and lymph node metastases survival rather than by enhancing primary tumor proliferation or therapy resistance.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
Document type specification: Scientific article
License: CC BY
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Journal: Cancers
Pages or article number: 2337
Publisher: MDPI
Publisher place: Basel
Issue date: 2022
ISSN: 2072-6694
Publisher DOI: 10.3390/cancers14092337
Appears in collections:DFG-491381577-G

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