Aurora-B dysfunction of multinucleated giant cells in glioma detected by site-specific phosphorylated antibodies
Aurora-B dysfunction of multinucleated giant cells in glioma detected by site-specific phosphorylated antibodies
复制标题
DOI：
10.3171/jns.2004.101.6.1012
复制
发表时间：
2004-12-01
影响因子：
4.1
通讯作者：
Yoshida, J
中科院分区：
文献类型：
--
作者：
Fujita, M;Mizuno, M;Yoshida, J
Object.胶质瘤中多核巨细胞的起源尚不清楚。在之前的论文中，作者通过使用有丝分裂特异性磷酸化抗体来确定中间丝的磷酸化来研究多核巨瘤细胞，并证明这些细胞停留在有丝分裂早期阶段，既不融合也不变性。在目前的研究中，作者调查了多核巨瘤细胞的可能遗传原因。用单克隆抗体（mAb）4A 4、YT 33、TM 71、HTA 28、YG 72和alphaAIM-1对培养的单核或多核人神经胶质瘤细胞进行免疫染色。前三种抗体通过波形蛋白的位点特异性磷酸化揭示了特定的有丝分裂细胞周期，即分别为早期、中期和晚期。后三种抗体分别证明了H3在Ser 28处的磷酸化、波形蛋白在Ser 72处的磷酸化和极光-B，使得有可能鉴定极光-B在有丝分裂期间的分布和功能。此外，我们还检测了3例巨细胞胶质母细胞瘤患者的石蜡包埋组织切片，在体外和体内，多核巨瘤细胞与mAb 4A 4和alphaAIM-1发生免疫反应，而与YT 33、TM 71、HTA 28和YG 72不发生免疫反应。这项研究的结果表明，由于极光-B功能障碍，多核巨瘤细胞仍处于有丝分裂早期，影响胞质分裂的畸变，而不影响核分裂。
Object. The origin of multinucleated giant cells in glioma has not been made clear. In a previous paper the authors studied multinucleated giant tumor cells by using mitosis-specific phosphorylated antibodies to determine the phosphorylation of intermediate filaments and demonstrated that these cells stay in the early mitotic stage, undergoing neither fusion nor degeneration. In the current study the authors investigated the possible genetic causes of multinucleated giant tumor cells.Methods. Cultured mono- or multinucleated human glioma cells were immunostained with monoclonal antibodies (mAbs) 4A4, YT33, TM71, HTA28, YG72, and alphaAIM-1. The three former antibodies revealed a particular mitotic cell cycle through site-specific phosphorylation of vimentin; that is, the early phase, mid phase, and late phase, respectively. The three later antibodies demonstrated phosphorylation of H3 at Ser28, phosphorylation of vimentin at Ser72, and aurora-B, respectively, making it possible to identify aurora-B distribution and function during mitosis. In addition, paraffin-embedded tissue sections obtained in three patients with giant cell glioblastoma were also examined.Multinucleated giant tumor cells immunoreacted with the mAb 4A4 and alphaAIM-1 but not with YT33, TM71, HTA28, and YG72 in vitro and in vivo.Conclusions. Findings in this study indicated that multinucleated giant tumor cells remain in the early mitotic phase because of aurora-B dysfunction, effecting aberrations in cytoplasmic cleavage without affecting nuclear division.