Development of a new radiosensitizer utilizing the cell specificity of exosomes

• Project/Area Number: 18K07676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Kobe University
• Principal Investigator: Inubushi Sachiko 神戸大学, 医学研究科, 特命講師 (60585959)
• Co-Investigator(Kenkyū-buntansha): 佐々木 良平 神戸大学, 医学部附属病院, 教授 (30346267) ; 宮脇 大輔 神戸大学, 医学部附属病院, 特命准教授 (30546502) ; 吉田 賢史 神戸大学, 医学部附属病院, 特命准教授 (80351906) ; 下野 洋平 藤田医科大学, 医学部, 教授 (90594630)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: エクソソーム / 放射線 / miRNA / 細胞外小胞体

Outline of Final Research Achievements

The precise mechanism of intercellular communication between cancer cells following radiation exposure is unclear. The present study aimed to identify novel roles of exosomes released from irradiated cells to neighboring cancer cells.Further analysis using miRNA mimics and reverse transcription-quantitative PCR identified miR-6823-5p as a potential candidate to inhibit SOD1, leading to increased intracellular ROS levels and DNA damage. The present study is the first to demonstrate that irradiated exosomes enhance the radiation effect via increasing intracellular ROS levels in cancer cells.

Academic Significance and Societal Importance of the Research Achievements

本研究はエクソソームを利用した放射線増感剤の開発のための基礎研究である。これまで放射線増感剤の研究は多くなされてきたが、臓器ターゲティング効果という点で多くの問題があった。本研究により、エクソソームを利用した新たな放射線増感剤の開発に向けた大きな一歩となり得ると言える。

Research Products

• [Journal Article] Exosome-mediated radiosensitizing effect on neighboring cancer cells via increase in intracellular levels of reactive oxygen species (2021)
  • Author(s): Nakaoka Ai、Nakahana Makiko、Inubushi Sachiko、Akasaka Hiroaki、Salah Mohammed、Fujita Yoshiko、Kubota Hikaru、Hassan Mennaallah、Nishikawa Ryo、Mukumoto Naritoshi、Ishihara Takeaki、Miyawaki Daisuke、Sasayama Takashi、Sasaki Ryohei
  • Journal Title: Oncology Reports Volume: 45 Issue: 4 Pages: 1-1
  • DOI: 10.3892/or.2021.7964
  • NAID: 120006975755
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Bystander effect of exosomes derived from cervical adenocarcinoma cells in response to irradiation (2018)
  • Author(s): Sachiko Inubushi, Yoshiko Fujita, Sasaki Ryohei
  • Organizer: ISEV2018 - International Society for Extracellular Vesicles
  • Int'l Joint Research
• [Presentation] 放射線照射によって分泌された子宮頸部腺がん細胞由来エクソソームのBystander効果の検討 (2018)
  • Author(s): 犬伏祥子、藤田佳子、佐々木良平
  • Organizer: 第１０回日本ＲＮＡｉ研究会 第５回日本細胞外小胞学会JSEV