Oncotarget

Research Papers:

Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2

Benjamin M. Wahle, Eric T. Hawley, Yongzheng He, Abbi E. Smith, Jin Yuan, Andi R. Masters, David R. Jones, Jeffrey R. Gehlhausen, Su-Jung Park, Simon J. Conway, D. Wade Clapp _ and Charles W. Yates

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Oncotarget. 2018; 9:718-725. https://doi.org/10.18632/oncotarget.22002

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Abstract

Benjamin M. Wahle1,2, Eric T. Hawley1, Yongzheng He1, Abbi E. Smith1, Jin Yuan1, Andi R. Masters3, David R. Jones3, Jeffrey R. Gehlhausen1, Su-Jung Park1, Simon J. Conway1, D. Wade Clapp1 and Charles W. Yates1,2

1Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA

2Department of Otolaryngology/Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA

3Clinical Pharmacology Analytical Core, Indiana University Simon Cancer Center, Indianapolis, Indiana, USA

Correspondence to:

D. Wade Clapp, email: [email protected]

Charles W. Yates, email: [email protected]

Keywords: neurofibromatosis type 2; vestibular schwannoma; cyclooxygenase 2; non-steroidal anti-inflammatory agents; transgenic mice

Abbreviations: COX-2 (cyclooxygenase-2), NSAID (nonsteroidal antiinflamatory drug)

Received: March 31, 2017     Accepted: October 02, 2017     Published: October 24, 2017

ABSTRACT

Mutations in the tumor suppressor gene NF2 lead to Neurofibromatosis type 2 (NF2), a tumor predisposition syndrome characterized by the development of schwannomas, including bilateral vestibular schwannomas with complete penetrance. Recent work has implicated the importance of COX-2 in schwannoma growth. Using a genetically engineered murine model of NF2, we demonstrate that selective inhibition of COX-2 with celecoxib fails to prevent the spontaneous development of schwannomas or sensorineural hearing loss in vivo, despite elevated expression levels of COX-2 in Nf2-deficient tumor tissue. These results suggest that COX-2 is nonessential to schwannomagenesis and that the proposed tumor suppressive effects of NSAIDs on schwannomas may occur through COX-2 independent mechanisms.


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