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Functional analysis of KIF20A, a potential immunotherapeutic target for glioma

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Abstract

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.

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Acknowledgements

We thank Ms. Y. Aikawa, Ms. N. Tsuzaki, and Ms. K. Koide for technical assistance. This research was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (B), Grant Number 22390283.

Author contributions

Conceived and designed the experiments: KS, SO, YK, KS, and MT. Performed the experiments:KS, SO. Analyzed the data KS: Contributed reagents/materials/analysis tools: SO, YK, KS, and MT. Wrote the paper: KS, SO, and MT.

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Authors and Affiliations

  1. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Katsuya Saito, Kazunari Yoshida & Masahiro Toda

  2. Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Shigeki Ohta & Yutaka Kawakami

Authors
  1. Katsuya Saito
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  2. Shigeki Ohta
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Correspondence to Masahiro Toda.

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11060_2016_2360_MOESM1_ESM.tif

In silico analysis of REMBRANDT dataset, showing correlation between glioma patient overall survival and KIF20A expression. The relationship between patient prognosis and expression intensity of the target gene was analyzed in silico using the GlioVis portal (http://gliovis.bioinfo.cnio.es). Red line indicates high KIF20A expression (n=199), and blue line indicates low KIF20A expression (n=198). Patients with high expression (red line) have significantly shorter survival than those with a low expression (blue line) level of KIF20A (TIF 3315 KB)

11060_2016_2360_MOESM2_ESM.tif

siRNAs effect on expression of KIF20A in glioma cells. a KIF20A expression was investigated 2 and 5 days after KIF20A siRNA transfection in SF126 glioma cells, compared with mock (untreated) and control siRNA treatment as assessed by western blot analysis. b KIF20A expression was investigated 5 days after KIF20A siRNA transfection in U251MG glioma cells and U87MG glioma-like cells, compared with control siRNA treatment as assessed by western blot analysis (TIF 7600 KB)

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Saito, K., Ohta, S., Kawakami, Y. et al. Functional analysis of KIF20A, a potential immunotherapeutic target for glioma. J Neurooncol 132, 63–74 (2017). https://doi.org/10.1007/s11060-016-2360-1

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  • DOI: https://doi.org/10.1007/s11060-016-2360-1

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