NLRP3 inflammasome activation in human vestibular schwannoma: Implications for tumor-induced hearing loss

Jessica E. Sagers, Mehmet I. Sahin, In Seok Moon, Sherif G. Ahmed, Anat Stemmer-Rachamimov, Gary J. Brenner, Konstantina M. Stankovic

Research output: Contribution to journalArticle

Abstract

Vestibular schwannoma (VS) is the fourth most common intracranial tumor, arising from neoplastic Schwann cells of the vestibular nerve and often causing debilitating sensorineural hearing loss (SNHL) and tinnitus. Previous research suggests that the abnormal upregulation of inflammatory pathways plays a highly significant, though infrequently described role in VS pathobiology, and that VS-associated SNHL is due not only to mechanical compression of the auditory nerve but also to differences in the intrinsic biology of these tumors. We hypothesize that patients who present with poor hearing associated with VS experience a more robust inflammatory response to this tumor than VS patients who present with good hearing. To investigate this hypothesis, we conducted a comprehensive pathway analysis using gene expression data from the largest meta-analysis of vestibular schwannoma microarray data, comprising 80 tumors and 16 healthy peripheral nerves. We identified the NLRP3 inflammasome as a novel target worthy of further exploration in VS research and validated this finding at the gene and protein expression level in human VS tissue using qRT-PCR and immunohistochemistry. To date, NLRP3 inflammasome activation has not been reported in VS, and this finding may represent a new and potentially significant therapeutic avenue. Notably, after analysis of 30 VSs, we observe that overexpression of key components of the NLRP3 inflammasome is preferentially associated with tumors that produce increased hearing loss in VS patients. Therefore, therapeutic development for VS should include considerations for minimizing NLRP3-associated inflammation to best preserve hearing.

Original languageEnglish
Article number107770
JournalHearing Research
Volume381
DOIs
Publication statusPublished - 2019 Sep 15

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Inflammasomes
Acoustic Neuroma
Hearing Loss
Neoplasms
Hearing
Sensorineural Hearing Loss
Vestibular Nerve
Gene Expression
Cochlear Nerve
Tinnitus
Schwann Cells
Peripheral Nerves
Research
Meta-Analysis
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Sensory Systems

Cite this

Sagers, J. E., Sahin, M. I., Moon, I. S., Ahmed, S. G., Stemmer-Rachamimov, A., Brenner, G. J., & Stankovic, K. M. (2019). NLRP3 inflammasome activation in human vestibular schwannoma: Implications for tumor-induced hearing loss. Hearing Research, 381, [107770]. https://doi.org/10.1016/j.heares.2019.07.007
Sagers, Jessica E. ; Sahin, Mehmet I. ; Moon, In Seok ; Ahmed, Sherif G. ; Stemmer-Rachamimov, Anat ; Brenner, Gary J. ; Stankovic, Konstantina M. / NLRP3 inflammasome activation in human vestibular schwannoma : Implications for tumor-induced hearing loss. In: Hearing Research. 2019 ; Vol. 381.
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NLRP3 inflammasome activation in human vestibular schwannoma : Implications for tumor-induced hearing loss. / Sagers, Jessica E.; Sahin, Mehmet I.; Moon, In Seok; Ahmed, Sherif G.; Stemmer-Rachamimov, Anat; Brenner, Gary J.; Stankovic, Konstantina M.

In: Hearing Research, Vol. 381, 107770, 15.09.2019.

Research output: Contribution to journalArticle

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AU - Ahmed, Sherif G.

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