In vivo imaging system of cancer-derived exosome using a BRET reporter

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: HIKITA TOMOYA 愛知県がんセンター(研究所), 腫瘍制御学分野, 研究員 (20600935)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: エクソソーム / がん / 生体イメージング / BRETレポーター

Outline of Final Research Achievements

The long-term monitoring of exosome dynamics in living organisms is essential to demonstrate real functions of cancer-derived exosomes. However, various experimental limitations have made it impossible. Im this study, we developed the exosome-tracking mice model using bioluminescence resonance energy transfer (BRET). Transplantation of CD63-red-shifted reporter-expressing cells made it possible to monitor the amounts of cancer-derived exosomes released from primary tumor into the bloodstream, and to identify the exosome-mediated long-term homing behavior in certain organs or tissues. Furthermore, the exosome-derived luminescence in blood and tissues was attenuated by administrating the tyrosine-kinase inhibitor dasatinib. Therefore, CD63-red-shifted reporter xenograft mice model would be a useful tool for elucidating the dynamics of cancer-derived exosomes and evaluating the effects of exosome inhibitors.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

がん細胞は、エクソソームを介して近くや遠くの細胞へ作用し、腫瘍の増大やがん転移に有利な環境を作り出す。このため、がん細胞が産生するエクソソーム量やその集積組織を生体レベルで解析することは非常に重要である。しかし、エクソソームはナノサイズの微細な構造体であるため、これらの解析が非常に困難であった。本研究で構築した生体イメージング系は、高感度かつ定量的に生体内のがんエクソソーム量や集積組織の同定を可能とし、生体におけるエクソソームの機能解析や阻害薬開発の有用なツールとして高い利用価値を有する。