Does NANOG have the potential to regulate immune escape of cancer stem cells?

• Project/Area Number: 16K15236
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University
• Principal Investigator: Kaneda Yasufumi 大阪大学, 医学系研究科, 教授 (10177537)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌幹細胞 / Nanog / NK細胞 / がん幹細胞 / ICAM-1 / Nk細胞 / 癌

Outline of Final Research Achievements

In cancer stem-like cells, high expression of Nanog and low expression of ICAM-1 were discovered. Nanog expression inhibited ICAM-1 expression in cancer cells, which suppressed the sensitivity of cancer cells to NK cells. Xenograft experiments were performed in SCID mice using cancer cells with Nanog-overexpression or Nanog suppression by Nanog shRNA. It was concluded that Nanog expression accelerated tumor growth in mice by lowering NK cell sensitivity through the suppression of ICAM-1. ChIP seq analysis revealed that Nanog bound to the ICAM-1 promoter sited and inhibited the association of histone acetylase p300 with ICAM-1 promoter. Clinical sample analysis demonstrated the inverse correlation of Nanog and ICAM-1 expression.

Research Products

• [Journal Article] Inactivated Sendai Virus Particles upregulate cancer cell ICAM-1 expression with enhancing NK cell sensitivity on cancer cell. (2017)
  • Author(s): Simin, L., Nishikawa, T., Kaneda, Y.
  • Journal Title: Cancer Science Volume: 108 Issue: 12 Pages: 2333-2341
  • DOI: 10.1111/cas.13408
  • Peer Reviewed / Open Access
• [Journal Article] Salmonella mediated the hemagglutinating virus of Japan-envelope transfer suppresses tumor growth. (2017)
  • Author(s): Lee C-H, Nishikawa, T., Kaneda, Y.
  • Journal Title: Oncotarget Volume: 8 Issue: 21 Pages: 35048-35060
  • DOI: 10.18632/oncotarget.17037
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phase I/II clinical trial to assess safety and efficacy of intratumoral and subcutaneous injection of HVJ-E to castration resistant prostate cancer patients. (2017)
  • Author(s): Fujita, K., Nakai, Y., Kawashima, A., Ujike, T., Nagahara, A., Uemura, M., Miyagawa Y., Lee, C-M., Inoue, T., Kaneda, Y., Nonomura, I.
  • Journal Title: Cancer Gene Therapy Volume: 24 Issue: 7 Pages: 277-281
  • DOI: 10.1038/cgt.2017.15
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of alternative polyadenylation by Nkx2-5 and Xrn2 during mouse heart development. (2016)
  • Author(s): Nimura K, Yamamoto M, Takeichi M, Saga K, Takaoka K, Kawamura N, Nitta H, Nagano H, Ishino S, Tanaka T, Schwartz RJ, Aburatani H, Kaneda Y.
  • Journal Title: Elife. Volume: 22;5 Pages: 1-20
  • DOI: 10.7554/elife.16030
  • NAID: 120006976062
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Clinical trials for the treatment of intractable cancers using HVJ envelope (HVJ-E). (2017)
  • Author(s): Kaneda, Y.
  • Organizer: 第76回日本癌学会学術総会,
• [Presentation] Current status and future prospect of gene therapy in Japan. (2017)
  • Author(s): Kaneda, Y.
  • Organizer: 第23回日本遺伝子細胞治療学会学術集会
• [Presentation] Current status and future prospect of human gene therapy (2017)
  • Author(s): Kaneda, Y.
  • Organizer: 国際胎児新生児治療学会2017
  • Int'l Joint Research / Invited
• [Presentation] 世界の遺伝子治療の現状と展望 (2017)
  • Author(s): 金田安史
  • Organizer: 日本人類遺伝学会第62回大会
  • Invited