Exploring mechanisms for determining exosome destination

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16538
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Gifu University
• Principal Investigator: Yamada Nami 岐阜大学, 大学院医学系研究科, 助教 (40727319)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: エクソソーム / 細胞間コミュニケーション

Outline of Final Research Achievements

Recent studies have revealed that cancer cells secrete extracellular vesicles (EVs) to communicate with surrounding cells in the tumor microenvironment. We have focused on the roles of microRNAs packed within the EVs secreted by colorectal cancer (CRC) cells. In the process, we obtained a suggestive finding that EVs were not secreted at random but had a specific destination. Therefore, in this study we explored proteins and mechanisms for determining EV's destination.
We identified 154 proteins contained within the CRC cell-derived EVs by LC-MS/MS. We further studied structure and function of each protein, and narrowed down the candidates to 67 proteins. Detailed function of each protein in vitro is now being analyzed.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は「エクソソームに宛先があること」および「がん転移には臓器指向性があること」の共通点に着眼し、新たな視点から「Seed and Soil説」の分子メカニズムにアプローチする研究である。すなわちがん転移の分子病態がエクソソームの観点より明らかになることで、がんの転移兆候を早期診断し、転移予防や転移抑制のための治療戦略を立てることに貢献できる可能性がある。具体的には、がんが分泌した転移促進エクソソームを透析に近い形で体液中より除去する方法の開発や、がんが分泌したエクソソームの宛先を取り払い、尿中へ排泄してしまう方法の開発など、発展が期待できる。