title: Secreted Factors from Human Vestibular Schwannomas Can Cause Cochlear Damage.
abstract: Vestibular schwannomas (VSs) are the most common tumours of the cerebellopontine angle. Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. To establish the first model to study the role of VS-secreted factors in causing SNHL, murine cochlear explant cultures were treated with human tumour secretions from thirteen different unilateral, sporadic VSs of subjects demonstrating varied degrees of ipsilateral SNHL. The extent of cochlear explant damage due to secretion application roughly correlated with the subjects' degree of SNHL. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Secretions from VSs associated with good hearing or from healthy human nerves led to either no effect or solely fibre disorganization. Our results are the first to demonstrate that secreted factors from VSs can lead to cochlear damage. Further, we identified tumour necrosis factor alpha (TNFα) as an ototoxic molecule and fibroblast growth factor 2 (FGF2) as an otoprotective molecule in VS secretions. Antibody-mediated TNFα neutralization in VS secretions partially prevented hair cell loss due to the secretions. Taken together, we have identified a new mechanism responsible for SNHL due to VSs.
authors.affiliation: Eaton Peabody Laboratories, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.|Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.|Harvard-MIT Program in Health, Science and Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Sonam
authors.initials: S
authors.lastname: Dilwali
authors.affiliation: Eaton Peabody Laboratories, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.|Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.|Department of Otology and Laryngology, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: Lukas D
authors.initials: LD
authors.lastname: Landegger
authors.affiliation: Eaton Peabody Laboratories, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.|Department of Otology and Laryngology, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.|Department of Otorhinolaryngology-Head and Neck Surgery, Health Science Faculty, University of Brasilia, SGAN, Via L2 Norte, Quadra 604/605, 70840-050, Asa Norte, DF, Brazil.
authors.forename: Vitor Y R
authors.initials: VY
authors.lastname: Soares
authors.affiliation: Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.|Department of Otology and Laryngology, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Deschler
authors.affiliation: Eaton Peabody Laboratories, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.|Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.|Harvard-MIT Program in Health, Science and Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.|Department of Otology and Laryngology, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: Konstantina M
authors.initials: KM
authors.lastname: Stankovic
mesh_terms: D000328:Adult; D000818:Animals; D001301:Audiometry, Pure-Tone; D003051:Cochlea / Q000187:drug effects / Q000473:pathology*; D003710:Demography; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000150:complications; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D009464:Neuroma, Acoustic / Q000150:complications / Q000378:metabolism*; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor