Open Access

ADAM9: A novel player in vestibular schwannoma pathogenesis

  • Authors:
    • Maria Breun
    • Alexandra Schwerdtfeger
    • Donato Daniel Martellotta
    • Almuth F. Kessler
    • Camelia M. Monoranu
    • Cordula Matthies
    • Mario Löhr
    • Carsten Hagemann
  • View Affiliations

  • Published online on: January 14, 2020     https://doi.org/10.3892/ol.2020.11299
  • Pages: 1856-1864
  • Copyright: © Breun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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March 2020
Volume 19 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Breun, M., Schwerdtfeger, A., Martellotta, D.D., Kessler, A.F., Monoranu, C.M., Matthies, C. ... Hagemann, C. (2020). ADAM9: A novel player in vestibular schwannoma pathogenesis. Oncology Letters, 19, 1856-1864. https://doi.org/10.3892/ol.2020.11299
MLA
Breun, M., Schwerdtfeger, A., Martellotta, D. D., Kessler, A. F., Monoranu, C. M., Matthies, C., Löhr, M., Hagemann, C."ADAM9: A novel player in vestibular schwannoma pathogenesis". Oncology Letters 19.3 (2020): 1856-1864.
Chicago
Breun, M., Schwerdtfeger, A., Martellotta, D. D., Kessler, A. F., Monoranu, C. M., Matthies, C., Löhr, M., Hagemann, C."ADAM9: A novel player in vestibular schwannoma pathogenesis". Oncology Letters 19, no. 3 (2020): 1856-1864. https://doi.org/10.3892/ol.2020.11299