Development of peptide inhibitors targeting ADAM10 to eradicate brain tumor-initiating cells

• Project/Area Number: 26670650
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: IZAWA Ichiro 愛知県がんセンター(研究所), 腫瘍医化学部, 室長 (20311441)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ADAM10 / テトラスパニン

Outline of Final Research Achievements

In this study, to utilize for the therapeutic methods of malignant gliomas, we tried to develop peptide inhibitors targeting ADAM10, a membrane-bound protease. We found that ADAM10 binds Tspan14, a member of TspanC8 subgroup of tetraspanin membrane proteins, via three domains, leading to the bending of the extracellular portions of ADAM10. We observed that the recombinant GST fusion proteins of these three domains of ADAM10 which were exogenously added to the culture media might be able to inhibit the activity of ADAM10 in the U251MG cell culture.

Research Products

• [Journal Article] Current topics of functional links between primary cilia and cell cycle (2015)
  • Author(s): Izawa I., Goto H., Kasahara K., and Inagaki M.
  • Journal Title: Cilia Volume: 4 Issue: 1 Pages: 12-12
  • DOI: 10.1186/s13630-015-0021-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cytokinetic failure-induced tetraploidy develops into aneuploidy, triggering skin aging in phospho-vimentin deficient mice. (2015)
  • Author(s): Tanaka, H., Goto, H., Inoko, A., Makihara, H., Enomoto, A., Horimoto, K., Matsuyama, M., Kurita, K., Izawa, I., and Inagaki, M.
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 21 Pages: 12984-12998
  • DOI: 10.1074/jbc.m114.633891
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 細胞周期とがん． (2015)
  • Author(s): 稲垣昌樹, 井澤一郎．
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-10
  • Invited
• [Presentation] ビメンチンリン酸化不全マウスの皮膚線維芽細胞は染色体異数性を呈し、皮膚の早期老化を示す． (2015)
  • Author(s): 田中宏樹, 後藤英仁, 猪子誠人, 牧原弘幸, 榎本篤, 井澤一郎, 稲垣昌樹．
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-08
• [Presentation] ビメンチンリン酸化不全変異マウスにおける染色体不安定性と老化. (2015)
  • Author(s): 牧原弘幸, 田中宏樹, 後藤英仁, 猪子誠人, 榎本篤, 後藤満雄, 栗田賢一, 井澤一郎, 稲垣昌樹．
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2015-06-30
• [Presentation] 分裂期ビメンチンリン酸化不全マウスは染色体異数性と老化を引き起こす (2014)
  • Author(s): 田中宏樹、後藤英仁、猪子誠人、井澤一郎、稲垣昌樹
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-09-27
• [Presentation] Phosphorylation-deficient vimentin mutant mice develop premature aging via aneuploidy and cellular senescence (2014)
  • Author(s): Tanaka, H., Goto, H., Inoko, A., Makihara, H., Izawa, I., and Inagaki, M.
  • Organizer: Gordon Research Conference - Intermediate Filaments
  • Place of Presentation: West Dover, VT, USA
  • Year and Date: 2014-06-15 – 2014-06-20
• [Remarks] 愛知県がんセンターホームページ
  • URL: http://www.pref.aichi.jp/cancer-center