听神经瘤S518磷酸化Merlin蛋白的表达及与CD44结合特性

Expression of S518 phosphorylated Merlin and its interaction with CD44 in vestibular schwannoma

目的探讨听神经瘤组织中S518磷酸化对Merlin蛋白与细胞表面糖蛋白CD44结合能力的影响及其与肿瘤生长的关系。方法35例听神经瘤组织标本均经过病理学证实，用免疫组织化学技术和免疫印迹技术分析S518磷酸化Merlin蛋白的表达、组织学分布情况，以手术中切除的正常颅神经作对照。将各标本中S518磷酸化Merlin条带的相对灰度值与听神经瘤临床分期、瘤体大小、病程及囊性变进行相关分析。用免疫沉淀技术比较野生型Merlin蛋白及S518磷酸化Merlin蛋白与CD44结合能力的差异。结果在听神经瘤组织中Merlin蛋白发生S518磷酸化且分布集中于核周；正常对照神经组织中Merlin也发生S518磷酸化，但是其含量较听神经瘤组织低。S518磷酸化的Merlin蛋白在听神经瘤组织中的表达量与临床分期、肿瘤大小、病程及囊性变之间无统计学相关关系。在听神经瘤组织中，与S518磷酸化的Merlin蛋白结合的CD44量高于与野生型Merlin蛋白结合的CD44的量。结论在听神经瘤组织中，S518磷酸化的Merlin蛋白与CD44的结合能力增加，CD44与野生型Merlin蛋白和S518磷酸化Merlin蛋白结合后可能产生不同细胞生物学行为。

Objective To investigate the impact of S518 phosphorylation in Merlin on the interaction with CD44 in vestibular schwannoma and the tumor growth. Methods Thirty-five samples of vestibular schwannoma were identified by pathology. Immunohistopathology and western blot were employed to analyze the expression and localization of S518 phosphorylated Merlin in the tumor tissues. Nerve tissues that were collected during other surgical operation were used as control. The expression level of S518 phosphorylated Merlin was compared with clinical stages, tumor size, clinical course and cystic degeneration, Immunoprecipitation was used to evaluate the impact of S518 phosphorylation in Merlin on the interaction with CD44. Results In vestibular schwannoma, Merlin was phosphorylated at S518 and demonstrated perinuclear localization. The S518 phosphorylation level was much lower in the normal control nerve tissues than that in vestibular schwannoma tissues. There was no correlation between the phosphorylation level on Merlin and clinical stages, tumor size, clinical course and cystic degeneration. The S518 phospborylated Merlin bound CD44 was higher than wild-type Merlin bound CD44 in vestibular schwannoma tissues. Conclusions The affinity of Merlin to CD44 was increased after phosphorylation at S518. Different cellular biological results might be triggered through binding to wild type Merlin and S518 phosphorylated Merlin.