Journal article
Effects of Neurod1 Expression on Mouse and Human Schwannoma Cells
The Laryngoscope, Vol.131(1), pp.E259-E270
05/21/2020
DOI: 10.1002/lary.28671
PMCID: PMC7772964
PMID: 32438526
Abstract
Objectives
The objective was to explore the effect of the proneuronal transcription factor neurogenic differentiation 1 (Neurod1, ND1) on Schwann cells (SC) and schwannoma cell proliferation.
Methods
Using a variety of transgenic mouse lines, we investigated how expression of Neurod1 effects medulloblastoma (MB) growth, schwannoma tumor progression, vestibular function, and SC cell proliferation. Primary human vestibular schwannoma (VS) cell cultures were transduced with adenoviral vectors expressing Neurod1. Cell proliferation was assessed by 5‐ethynyl‐2'‐deoxyuridine (EdU) uptake.
Study Design
Basic science investigation.
Results
Expression of Neurod1 reduced the growth of slow‐growing but not fast‐growing MB models. Gene transfer of Neurod1 in human schwannoma cultures significantly reduced cell proliferation in dose‐dependent way. Deletion of the neurofibromatosis type 2 (Nf2) tumor‐suppressor gene via Cre expression in SCs led to increased intraganglionic SC proliferation and mildly reduced vestibular sensory‐evoked potentials (VsEP) responses compared to age‐matched wild‐type littermates. The effect of Neurod1‐induced expression on intraganglionic SC proliferation in animals lacking Nf2 was mild and highly variable. Sciatic nerve axotomy significantly increased SC proliferation in wild‐type and Nf2‐null animals, and expression of Neurod1 reduced the proliferative capacity of both wild‐type and Nf2‐null SCs following nerve injury.
Conclusion
Expression of Neurod1 reduces slow‐growing MB progression and reduces human SC proliferation in primary VS cultures. In a genetic mouse model of schwannomas, we find some effects of Neurod1 expression; however, the high variability indicates that more tightly regulated Neurod1 expression levels that mimic our in vitro data are needed to fully validate Neurod1 effects on schwannoma progression.
Details
- Title: Subtitle
- Effects of Neurod1 Expression on Mouse and Human Schwannoma Cells
- Creators
- Jennifer Kersigo - Department of BiologyUniversity of Lowa Lowa City Lowa U.S.ALintao Gu - Department of OtolaryngologyUniversity of Lowa Lowa City Lowa U.S.A., Decibel Pharmaceutical Boston Massachusetts U.S.ALinjing Xu - Department of OtolaryngologyUniversity of Lowa Lowa City Lowa U.S.ANing Pan - Department of BiologyUniversity of Lowa Lowa City Lowa U.S.A., Department of Special Education & Communication DisordersUniversity of Nebraska Lincoln Nebraska U.S.ASarath Vijayakuma - Department of OtolaryngologyThe First Affiliated Hospital of Shandong First Medical University Jinan, Shandong ChinaTimothy Jones - Department of OtolaryngologyThe First Affiliated Hospital of Shandong First Medical University Jinan, Shandong ChinaSeiji B Shibata - Department of OtolaryngologyUniversity of Lowa Lowa City Lowa U.S.ABernd Fritzsch - Department of BiologyUniversity of Lowa Lowa City Lowa U.S.A., Department of OtolaryngologyUniversity of Lowa Lowa City Lowa U.S.AMarlan R Hansen - Department of OtolaryngologyUniversity of Lowa Lowa City Lowa U.S.A
- Resource Type
- Journal article
- Publication Details
- The Laryngoscope, Vol.131(1), pp.E259-E270
- DOI
- 10.1002/lary.28671
- PMID
- 32438526
- PMCID
- PMC7772964
- NLM abbreviation
- Laryngoscope
- ISSN
- 0023-852X
- eISSN
- 1531-4995
- Grant note
- This work was supported by grants from The Roy J. and Lucille A. Carver College of Medicine, the University of Iowa, Iowa City, Iowa, U.S.A.; and the National Center for Advancing Translational Sciences (NCATS) (grants UL1TR002537 and R01 AG060504)
- Language
- English
- Date published
- 05/21/2020
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center; Neurosurgery; Otolaryngology
- Record Identifier
- 9984070541802771
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