Cargando…

ADAM9: A novel player in vestibular schwannoma pathogenesis

A disintegrin and metalloproteinase 9 (ADAM9) is a member of the transmembrane ADAM family. It is expressed in different types of solid cancer and promotes tumor invasiveness. To the best of our knowledge, the present study was the first to examine ADAM9 expression in vestibular schwannomas (VS) fro...

Descripción completa

Detalles Bibliográficos
Autores principales: Breun, Maria, Schwerdtfeger, Alexandra, Martellotta, Donato Daniel, Kessler, Almuth F., Monoranu, Camelia M., Matthies, Cordula, Löhr, Mario, Hagemann, Carsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039135/
https://www.ncbi.nlm.nih.gov/pubmed/32194680
http://dx.doi.org/10.3892/ol.2020.11299
_version_ 1783500766905892864
author Breun, Maria
Schwerdtfeger, Alexandra
Martellotta, Donato Daniel
Kessler, Almuth F.
Monoranu, Camelia M.
Matthies, Cordula
Löhr, Mario
Hagemann, Carsten
author_facet Breun, Maria
Schwerdtfeger, Alexandra
Martellotta, Donato Daniel
Kessler, Almuth F.
Monoranu, Camelia M.
Matthies, Cordula
Löhr, Mario
Hagemann, Carsten
author_sort Breun, Maria
collection PubMed
description A disintegrin and metalloproteinase 9 (ADAM9) is a member of the transmembrane ADAM family. It is expressed in different types of solid cancer and promotes tumor invasiveness. To the best of our knowledge, the present study was the first to examine ADAM9 expression in vestibular schwannomas (VS) from patients with and without neurofibromatosis type 2 (NF2) and to associate the data with clinical parameters of the patients. The aim of the present study was to evaluate if ADAM9 could be used as prognostic marker or therapeutic target. ADAM9 mRNA and protein levels were measured in VS samples (n=60). A total of 30 of them were from patients with neurofibromatosis. Healthy peripheral nerves from autopsies (n=10) served as controls. ADAM9 mRNA levels were measured by PCR, and protein levels were determined by immunohistochemistry (IHC) and western blotting (WB). The Hannover Classification was used to categorize tumor extension and hearing loss. ADAM9 mRNA levels were 8.8-fold higher in VS compared with in controls. The levels were 5.6-fold higher in patients with NF2 and 12-fold higher in patients with sporadic VS. WB revealed two mature isoforms of the protein, and according to IHC ADAM9 was mainly expressed by S100-positive Schwann cells. There was a strong correlation between ADAM9 mRNA expression and the level of functional impairment (r~1, p=0.01). Particularly, the secreted isoform of ADAM9 was expressed in patients with higher hearing impairment. ADAM9 mRNA was overexpressed in the tumor samples relative to healthy vestibular nerves, and there was an association between higher ADAM9 expression levels and greater hearing impairment. Therefore, ADAM9 may be a prognostic marker for VS, and ADAM9 inhibition might have the potential as a systemic approach for the treatment of VS.
format Online
Article
Text
id pubmed-7039135
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-70391352020-03-19 ADAM9: A novel player in vestibular schwannoma pathogenesis Breun, Maria Schwerdtfeger, Alexandra Martellotta, Donato Daniel Kessler, Almuth F. Monoranu, Camelia M. Matthies, Cordula Löhr, Mario Hagemann, Carsten Oncol Lett Articles A disintegrin and metalloproteinase 9 (ADAM9) is a member of the transmembrane ADAM family. It is expressed in different types of solid cancer and promotes tumor invasiveness. To the best of our knowledge, the present study was the first to examine ADAM9 expression in vestibular schwannomas (VS) from patients with and without neurofibromatosis type 2 (NF2) and to associate the data with clinical parameters of the patients. The aim of the present study was to evaluate if ADAM9 could be used as prognostic marker or therapeutic target. ADAM9 mRNA and protein levels were measured in VS samples (n=60). A total of 30 of them were from patients with neurofibromatosis. Healthy peripheral nerves from autopsies (n=10) served as controls. ADAM9 mRNA levels were measured by PCR, and protein levels were determined by immunohistochemistry (IHC) and western blotting (WB). The Hannover Classification was used to categorize tumor extension and hearing loss. ADAM9 mRNA levels were 8.8-fold higher in VS compared with in controls. The levels were 5.6-fold higher in patients with NF2 and 12-fold higher in patients with sporadic VS. WB revealed two mature isoforms of the protein, and according to IHC ADAM9 was mainly expressed by S100-positive Schwann cells. There was a strong correlation between ADAM9 mRNA expression and the level of functional impairment (r~1, p=0.01). Particularly, the secreted isoform of ADAM9 was expressed in patients with higher hearing impairment. ADAM9 mRNA was overexpressed in the tumor samples relative to healthy vestibular nerves, and there was an association between higher ADAM9 expression levels and greater hearing impairment. Therefore, ADAM9 may be a prognostic marker for VS, and ADAM9 inhibition might have the potential as a systemic approach for the treatment of VS. D.A. Spandidos 2020-03 2020-01-14 /pmc/articles/PMC7039135/ /pubmed/32194680 http://dx.doi.org/10.3892/ol.2020.11299 Text en Copyright: © Breun et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Breun, Maria
Schwerdtfeger, Alexandra
Martellotta, Donato Daniel
Kessler, Almuth F.
Monoranu, Camelia M.
Matthies, Cordula
Löhr, Mario
Hagemann, Carsten
ADAM9: A novel player in vestibular schwannoma pathogenesis
title ADAM9: A novel player in vestibular schwannoma pathogenesis
title_full ADAM9: A novel player in vestibular schwannoma pathogenesis
title_fullStr ADAM9: A novel player in vestibular schwannoma pathogenesis
title_full_unstemmed ADAM9: A novel player in vestibular schwannoma pathogenesis
title_short ADAM9: A novel player in vestibular schwannoma pathogenesis
title_sort adam9: a novel player in vestibular schwannoma pathogenesis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039135/
https://www.ncbi.nlm.nih.gov/pubmed/32194680
http://dx.doi.org/10.3892/ol.2020.11299
work_keys_str_mv AT breunmaria adam9anovelplayerinvestibularschwannomapathogenesis
AT schwerdtfegeralexandra adam9anovelplayerinvestibularschwannomapathogenesis
AT martellottadonatodaniel adam9anovelplayerinvestibularschwannomapathogenesis
AT kessleralmuthf adam9anovelplayerinvestibularschwannomapathogenesis
AT monoranucameliam adam9anovelplayerinvestibularschwannomapathogenesis
AT matthiescordula adam9anovelplayerinvestibularschwannomapathogenesis
AT lohrmario adam9anovelplayerinvestibularschwannomapathogenesis
AT hagemanncarsten adam9anovelplayerinvestibularschwannomapathogenesis