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

摘要: Vestibular schwannomas (VSs) are benign tumors that arise from the Schwann cells (SCs) lining vestibular nerve. VS survive and proliferate far neurons axonally derived growth factors. We have previously shown VSs produce glial factor, neuregulin-1 (NRG1), its receptors, ErbB2 ErbB3. In present work, we explore contribution of constitutive NRG1:ErbB signaling to human cell proliferation. confirm VSs, which express markers immature denervated SCs, also endogenous NRG1 activated ErbB2. find a blocking anti-NRG1 antibody trastuzumab (Herceptin®, HCN), humanized anti-ErbB2 inhibitory monoclonal antibody, effectively inhibit induced SC Treatment primary cultures with or HCN reduces proliferation in absence exogenous NRG1. Furthermore, conditioned medium contains stimulates cultures, an effect is inhibited by HCN. These data suggest autocrine pathway stimulation involving NRG ErbB receptors. Inhibition NRG:ErbB vitro may therapeutic potential for patients VSs. © 2005 Wiley-Liss, Inc.