Unveiling the epigenetic mechanism of cellular differentiation in undifferentiated canine hemangiosarcoma cells

• Project/Area Number: 18K14575
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Hokkaido University
• Principal Investigator: Aoshima Keisuke 北海道大学, 獣医学研究院, 助教 (90745069)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 血管肉腫 / エピジェネティクス / ヒストン脱メチル化 / 腫瘍 / イヌ / がん幹細胞

Outline of Final Research Achievements

We found that histone demethylase KDM2B highly expressed in canine hemangiosarcoma cell lines and clinical samples. KDM2B knockdown halted cell growth and induced apoptosis in vitro. Furthermore, KDM2B knockdown in the tumors inoculated in immunodeficient mice let the tumors started shrinking. Based on these results, we confirmed that KDM2B is responsible for tumor cell growth and survival.

Academic Significance and Societal Importance of the Research Achievements

本研究によりKDM2Bがイヌ血管肉腫の増殖・生存に必須であることが明らかとなった。イヌの血管肉腫は高頻度に発生する悪性腫瘍であるにも関わらず，現段階で有効な治療法がない。今回，免疫不全マウスを用いた実験で，KDM2Bノックダウンは血管肉腫を退縮させることが明らかとなった。このことは，KDM2Bが血管肉腫に対する有効な治療標的であることを示唆するものであり，血管肉腫の新たな治療法を開発する上での基礎となる研究成果である。今後はKDM2Bの役割を更に詳細に研究し，治療法開発に向けた知見を集める予定である。

Research Products

• [Journal Article] High drug efflux pump capacity and low DNA damage response induce doxorubicin resistance in canine hemangiosarcoma cell lines (2019)
  • Author(s): Morita Atsuya、Aoshima Keisuke、Gulay Kevin Christian Montecillo、Onishi Shinichi、Shibata Yuki、Yasui Hironobu、Kobayashi Atsushi、Kimura Takashi
  • Journal Title: Research in Veterinary Science Volume: 127 Pages: 1-10
  • DOI: 10.1016/j.rvsc.2019.09.011
  • NAID: 120006937029
  • Peer Reviewed
• [Presentation] The Role of Histone Lysine Demethylase 2B (KDM2B) in Endothelial Cell Carcinogenesis (2019)
  • Author(s): K.C.M. Gulay, K. Ashima, A. Kobayashi, and T. Kimura
  • Organizer: The 7th Sapporo Summer Symposium for One Health
  • Int'l Joint Research
• [Presentation] Analysis of the KDM2B-mediated Regulation of the Growth, Development, and Maintenance of Canine Hemangiosarcoma. (2018)
  • Author(s): Gulay, K.C.M., Aoshima, K., Kobayashi, A., and Kimura, T.
  • Organizer: The 6th SaSSOH seminar for One Health. Sapporo, Japan, 2018.
  • Int'l Joint Research
• [Presentation] Analysis of the KDM2B-mediated Regulation of the Growth, Development, and Maintenance of Canine Hemangiosarcoma (2018)
  • Author(s): Gulay, K.C.M., Aoshima, K., Kobayashi, A., and Kimura, T.
  • Organizer: 第41回 日本分子生物学会，横浜