Constitutive neuregulin-1/ErbB signaling contributes to human vestibular schwannoma proliferation

Marlan R Hansen; Pamela C Roehm; Papri Chatterjee; Steven H Green

doi:10.1002/glia.20316

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Constitutive neuregulin-1/ErbB signaling contributes to human vestibular schwannoma proliferation

Journal article

Peer reviewed

Constitutive neuregulin-1/ErbB signaling contributes to human vestibular schwannoma proliferation

Marlan R Hansen, Pamela C Roehm, Papri Chatterjee and Steven H Green

Glia, Vol.53(6), pp.593-600

04/15/2006

DOI: 10.1002/glia.20316

PMID: 16432850

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Abstract

Vestibular schwannomas (VSs) are benign tumors that arise from the Schwann cells (SCs) lining the vestibular nerve. VS cells survive and proliferate far from neurons and axonally derived growth factors. We have previously shown that VSs produce the glial growth factor, neuregulin-1 (NRG1), and its receptors, ErbB2 and ErbB3. In the present work, we explore the contribution of constitutive NRG1:ErbB signaling to human VS cell proliferation. We confirm that human VSs, which express markers of immature and denervated SCs, also express endogenous NRG1 and activated ErbB2. We find that a blocking anti-NRG1 antibody and trastuzumab (Herceptin, HCN), a humanized anti-ErbB2 inhibitory monoclonal antibody, effectively inhibit NRG1 induced SC proliferation. Treatment of primary VS cultures with anti-NRG1 or HCN reduces cell proliferation in the absence of exogenous NRG1. Furthermore, conditioned medium from VS cell cultures contains NRG1 and stimulates SC proliferation in SC cultures, an effect that is inhibited by anti-NRG1 and HCN. These data suggest an autocrine pathway of VS growth stimulation involving NRG and ErbB receptors. Inhibition of constitutive NRG:ErbB signaling reduces VS cell proliferation in vitro and may have therapeutic potential for patients with VSs.

Humans

Glycoproteins - metabolism

Culture Media, Conditioned - pharmacology

Autocrine Communication - drug effects

Oncogene Proteins v-erbB - metabolism

Stem Cells - metabolism

Neuregulin-1 - genetics

Cell Transformation, Neoplastic - genetics

Cell Differentiation - physiology

Gene Expression Regulation, Neoplastic - physiology

Schwann Cells - drug effects

Animals, Newborn

Biomarkers - metabolism

Autocrine Communication - physiology

Cells, Cultured

Rats

Vestibular Nerve - pathology

Schwann Cells - metabolism

Down-Regulation - drug effects

Cell Transformation, Neoplastic - metabolism

Cell Division - drug effects

Antibodies - pharmacology

Cell Division - physiology

Down-Regulation - physiology

Oncogene Proteins v-erbB - genetics

Animals

Cell Differentiation - drug effects

Neuroma, Acoustic - genetics

Neuregulin-1 - metabolism

Stem Cells - drug effects

Vestibular Nerve - physiopathology

Neuroma, Acoustic - pathology

Signal Transduction - physiology

Vestibular Nerve - metabolism

Cell Proliferation - drug effects

Neuroma, Acoustic - metabolism

Receptor, ErbB-2

Neuregulin-1 - antagonists & inhibitors

Details

Title: Subtitle: Constitutive neuregulin-1/ErbB signaling contributes to human vestibular schwannoma proliferation
Creators: Marlan R Hansen - Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, 52242, USA. marlan-hansen@uiowa.edu
Pamela C Roehm
Papri Chatterjee
Steven H Green
Resource Type: Journal article
Publication Details: Glia, Vol.53(6), pp.593-600
Publisher: United States
DOI: 10.1002/glia.20316
PMID: 16432850
ISSN: 0894-1491
eISSN: 1098-1136
Grant note: K08 DC006211-01A1 / NIDCD NIH HHS R01 DC002961 / NIDCD NIH HHS
Language: English
Date published: 04/15/2006
Academic Unit: Molecular Physiology and Biophysics; Biology; Neurosurgery; Otolaryngology
Record Identifier: 9984007187402771

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