Functional analysis of KIF20A, a potential immunotherapeutic target for glioma

• Published in: Journal of neuro-oncology 2017-03, Vol.132 (1), p.63-74
• Main Authors: Saito, Katsuya, Ohta, Shigeki, Kawakami, Yutaka, Yoshida, Kazunari, Toda, Masahiro
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - metabolism; Apoptosis; Brain - metabolism; Brain Neoplasms - immunology; Brain Neoplasms - metabolism; Cell Cycle; Cell Line, Tumor; Cell Survival; Glioma - immunology; Glioma - metabolism; Humans; Immunotherapy; Kinesin - metabolism; Laboratory Investigation; Medicine; Medicine & Public Health; Neurology; Oncology
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-016-2360-1

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.