Exosomal secretion of hypoxia-adapted multiple myeloma cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17388
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Toda Yuki 京都薬科大学, 薬学部, 助教 (40779724)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 低酸素 / Exosomes / HK2 / ミトコンドリア / 分泌制御機構

Outline of Final Research Achievements

Ineffectiveness of traditional therapies against cancer stem cells (CSCs) is reportedly associated with the poor outcome for multiple myeloma (MM) patients. Myeloma stem cells reside in hypoxic bone marrow niche where maintains their stem cell property. We previously established MM cells experienced long-term exposure of hypoxia and characterized their enhanced stem cell characteristics. The hypoxia-adapted (HA) cells require exosomal secretion for their survival in hypoxic condition. In this study, we identified Akt/AS160 signal as a regulatory signal for the exosome secretion and demonstrated mitochondrial localization of hexokinase 2 with anti-apoptotic function which was possibly involved in survival of HA-MM cells. The study provides insights in design novel therapy for prevention of recurrence resulting from myeloma stem cells.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

多発性骨髄腫（MM）の再発に関与する幹細胞性の高い集団（骨髄腫幹細胞）は、骨髄低酸素環境に存在すると言われている。代表者は、上記骨髄腫幹細胞を低酸素環境での長期培養によって再現し、その生存に細胞外小胞（exosomes）の分泌が関与することを見出した。さらに本課題ではその分泌制御に関わるシグナルおよび生存メカニズムの一部を明らかにした。本知見を基盤とする、骨髄腫幹細胞を標的とした再発を防ぐ治療法の開発が期待される。