Hansen Marlan R, Linthicum Fred H
Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA.
Otol Neurotol. 2004 Mar;25(2):155-9. doi: 10.1097/00129492-200403000-00013.
We sought to determine whether vestibular schwannomas are capable of producing and responding to the glial growth factor neuregulin.
Neuregulin is a neuronally derived trophic factor that interacts with erbB2 and erbB3 receptors on Schwann cells and is required for normal Schwann cell proliferation, survival, and development. Vestibular schwannomas grow several millimeters or even centimeters away from adjacent axons, suggesting that vestibular schwannomas do not depend critically on axons for their proliferation or survival. This raises the possibility that vestibular schwannomas themselves produce and respond to trophic factors in an autocrine fashion.
Pathologic specimens from eight patients undergoing microsurgical removal of vestibular schwannomas and one patient undergoing vestibular nerve section were immunostained with anti-neuregulin, anti-erbB2, anti-erbB3, and anti-phosphorylated-erbB2 antibodies. Three patients had received previous gamma knife radiation therapy and two patients had neurofibromatosis Type 2.
The Scarpa ganglion neurons express neuregulin, and normal vestibular Schwann cells express erbB2 and erbB3. Vestibular schwannomas from all eight patients demonstrated neuregulin, erbB2, and erbB3 immunoreactivity. In addition, all vestibular schwannomas demonstrated immunoreactivity to anti-phosphorylated-erbB2 antibody that only recognizes erbB2 when it is phosphorylated, or activated.
These results demonstrate that vestibular schwannomas express neuregulin and its receptors, erbB2 and erbB3. Because erbB2 exists in an activated state, as evidenced by phosphorylated-erbB2 immunoreactivity, it likely responds to the locally produced neuregulin. This suggests the possibility that vestibular schwannomas produce and respond to neuregulin in an autocrine fashion.
我们试图确定前庭神经鞘瘤是否能够产生并对神经胶质生长因子神经调节蛋白作出反应。
神经调节蛋白是一种源自神经元的营养因子，它与施万细胞上的erbB2和erbB3受体相互作用，是施万细胞正常增殖、存活和发育所必需的。前庭神经鞘瘤在距离相邻轴突数毫米甚至数厘米的地方生长，这表明前庭神经鞘瘤的增殖或存活并不严重依赖轴突。这就增加了前庭神经鞘瘤自身以自分泌方式产生并对营养因子作出反应的可能性。
对8例接受前庭神经鞘瘤显微手术切除的患者以及1例接受前庭神经切断术的患者的病理标本，用抗神经调节蛋白、抗erbB2、抗erbB3和抗磷酸化erbB2抗体进行免疫染色。3例患者先前接受过伽玛刀放射治疗，2例患者患有2型神经纤维瘤病。
斯卡帕神经节神经元表达神经调节蛋白，正常前庭施万细胞表达erbB2和erbB3。所有8例患者的前庭神经鞘瘤均显示神经调节蛋白、erbB2和erbB3免疫反应性。此外，所有前庭神经鞘瘤均显示对仅在磷酸化或激活时才识别erbB2的抗磷酸化erbB2抗体有免疫反应性。
这些结果表明前庭神经鞘瘤表达神经调节蛋白及其受体erbB2和erbB3。由于磷酸化erbB2免疫反应性证明erbB2处于激活状态，它可能对局部产生的神经调节蛋白作出反应。这提示前庭神经鞘瘤可能以自分泌方式产生并对神经调节蛋白作出反应。
