Saito Katsuya, Ohta Shigeki, Kawakami Yutaka, Yoshida Kazunari, Toda Masahiro
Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
J Neurooncol. 2017 Mar;132(1):63-74. doi: 10.1007/s11060-016-2360-1. Epub 2017 Jan 9.
Kinesin family member 20A (KIF20A), an ideal cancer-testis antigen, was reported to be a promising immunotherapeutic target for pancreatic cancers. Clinical trials of KIF20A peptide vaccine immunotherapy have been conducted against pancreatic cancers. To demonstrate the efficacy of KIF20A as a candidate molecular target for gliomas, we analyzed the expression and function of KIF20A in gliomas. Western blot and quantitative PCR analyses showed that KIF20A expression in glioma cell lines and glioma tissues was high compared with that found in a normal brain. KIF20A immunostaining of glioma cells and glioma tissues demonstrated that KIF20A was involved in spindle formation and cytokinesis, and that KIF20A was highly expressed, especially in glioma cells undergoing mitosis. In silico analysis of a cancer microarray database revealed that KIF20A was highly expressed in gliomas depending on the pathological grade, and glioma patients with higher expression of KIF20A showed poorer prognosis. Down-regulating KIF20A reduced cell proliferation in glioma cells due to the failure of cytokinesis and generation of binucleated cells. Additionally, KIF20A inhibition induced significant apoptosis in SF126 glioma cells. Taken together, KIF20A is a tumor-associated antigen involved in the glioma cell growth and cell survival, suggesting that KIF20A is an oncoantigen of gliomas. Thus, KIF20A is a candidate novel immunotherapeutic target for gliomas.
驱动蛋白家族成员20A（KIF20A）是一种理想的肿瘤睾丸抗原，据报道是胰腺癌有前景的免疫治疗靶点。针对胰腺癌的KIF20A肽疫苗免疫疗法的临床试验已经开展。为了证明KIF20A作为神经胶质瘤候选分子靶点的疗效，我们分析了KIF20A在神经胶质瘤中的表达和功能。蛋白质免疫印迹和定量PCR分析表明，与正常脑组织相比，神经胶质瘤细胞系和神经胶质瘤组织中KIF20A的表达较高。神经胶质瘤细胞和神经胶质瘤组织的KIF20A免疫染色表明，KIF20A参与纺锤体形成和胞质分裂，并且KIF20A高表达，尤其是在进行有丝分裂的神经胶质瘤细胞中。对癌症微阵列数据库的计算机分析显示，KIF20A在神经胶质瘤中的高表达取决于病理分级，KIF20A表达较高的神经胶质瘤患者预后较差。下调KIF20A会由于胞质分裂失败和双核细胞的产生而降低神经胶质瘤细胞的增殖。此外，抑制KIF20A会在SF126神经胶质瘤细胞中诱导明显的凋亡。综上所述，KIF20A是一种与肿瘤相关的抗原，参与神经胶质瘤细胞的生长和存活，这表明KIF20A是神经胶质瘤的一种癌抗原。因此，KIF20A是神经胶质瘤新型免疫治疗靶点的候选者。
