2021 Fiscal Year Final Research Report

Development of innovative cancer diagnostic and therapeutic seeds focusing on tissue specific exosomics using xenotransplantation model

Research Project

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Project/Area Number	18H04064
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Review Section	Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research Institution	Kyoto University
Principal Investigator	Ogawa Osamu 京都大学, 医学研究科, 名誉教授 (90260611)
Co-Investigator(Kenkyū-buntansha)	赤松秀輔京都大学, 医学研究科, 准教授 (20767248) 山崎俊成京都大学, 医学研究科, 講師 (00607749) 齊藤亮一京都大学, 医学研究科, 助教 (30792270)
Project Period (FY)	2018-04-01 – 2022-03-31
Keywords	エクソソーム / 患者癌組織由来ゼノグラフト / 腎細胞癌 / 薬剤抵抗性 / 転移形成 / 前転移ニッチ
Outline of Final Research Achievements	Intercellular communication between cancer cells and stromal cells is essential for drug resistance and metastasis formation of cancer, exosomes play a important role as messenger. In our study of drug resistance, exosomes secreted from sunitinib-resistant tumor have shown distinct miRNA profiles compared with control. Further study is required to elucidate the mechanism by which exosomes induce drug resistance. In our study of metastasis formation, we established a bone metastatic RCC cell line. Treatment of mice with exosomes collected from culture supernatant of bone metastatic RCC cells promoted angiogenesis in bone in a time-dependent manner and increased bone metastasis. We showed that exosomal CD13 contributed to angiogenesis. In addition, exosomes from bone metastatic RCC contained abundant CD13 and promoted angiogenesis compared with exosomes from RCC without metastasis. Our findings provide a new insight to the role of exosome in cancer metastasis and drug resistance.
Free Research Field	泌尿器癌
Academic Significance and Societal Importance of the Research Achievements	本研究により、エクソソームが時間依存性に腎癌骨転移の前転移ニッチを形成することが示された。また薬剤抵抗性腫瘍でエクソソーム中のmiRNAプロファイルは異なり、癌の薬剤抵抗性や転移形成の腫瘍間質相互作用にエクソソームが関わっていることが示唆された。今回の研究成果により、転移や薬剤抵抗性機序の解明につながるのみならず、エクソソームを転移予測のバイオマーカーに用いたり、治療抵抗性克服の治療ターゲットとするなど、臨床応用につながることが期待される。