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Journal of Neuro-Oncology

, Volume 133, Issue 2, pp 297–307 | Cite as

Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells

  • Ryogo Kikuchi
  • Oltea Sampetrean
  • Hideyuki Saya
  • Kazunari Yoshida
  • Masahiro TodaEmail author
Laboratory Investigation

Abstract

DEP domain containing 1 (DEPDC1) is a novel oncoantigen expressed in cancer cells, which presents oncogenic activity and high immunogenicity. Although DEPDC1 has been predicted to be a useful antigen for the development of a cancer vaccine, its pathophysiological roles in glioma have not been investigated. Here, we analyzed the expression and function of DEPDC1 in malignant glioma. DEPDC1 expression in glioma cell lines, glioma tissues, and brain tumor initiating cells (BTICs) was assessed by western blot and quantitative polymerase chain reaction (PCR). The effect of DEPDC1 downregulation on cell growth and nuclear factor kappa B (NFκB) signaling in glioma cells was investigated. Overall survival was assessed in mouse glioma models using human glioma cells and induced mouse brain tumor stem cells (imBTSCs) to determine the effect of DEPDC1 suppression in vivo. DEPDC1 expression was increased in glioma cell lines, tissues, and BTICs. Suppression of endogenous DEPDC1 expression by small interfering RNA (siRNA) inhibited glioma cell viability and induced apoptosis through NFκB signaling. In mouse glioma models using human glioma cells and imBTSCs, downregulation of DEPDC1 expression prolonged overall survival. These results suggest that DEPDC1 represents a target molecule for the treatment of glioma.

Keywords

DEPDC1 Oncoantigen Malignant glioma Vaccine therapy Molecular target therapy 

Notes

Acknowledgements

We thank Ms. Yuko Aikawa, Tomoko Muraki, and Naoko Tsuzaki (Department of Neurosurgery, Keio University School of Medicine) for technical assistance.

Funding

This research was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (B), Grant Number 15K19979.

Compliance with ethical standards

Conflict of interest

The author(s) declare that they have no competing interests.

Supplementary material

11060_2017_2457_MOESM1_ESM.pptx (23.3 mb)
Supplementary material 1 (PPTX 23824 KB)
11060_2017_2457_MOESM2_ESM.docx (27 kb)
Supplementary material 2 (DOCX 26 KB)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of NeurosurgeryKeio University School of MedicineTokyoJapan
  2. 2.Division of Gene Regulation, Institute for Advanced Medical ResearchKeio University School of MedicineTokyoJapan

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