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2020 Fiscal Year Final Research Report

New strategy of hepatocellular carcinoma treatment using exosomes exocrimned by cancer associated fibroblast

Research Project

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Project/Area Number 18K08707
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKyushu University

Principal Investigator

HARADA Noboru  九州大学, 大学病院, 講師 (80419580)

Co-Investigator(Kenkyū-buntansha) 間野 洋平  独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 肝胆膵外科医師 (10792244)
副島 雄二  信州大学, 学術研究院医学系, 教授 (30325526)
戸島 剛男  九州大学, 大学病院, 助教 (40608965)
本村 貴志  九州大学, 医学研究院, 共同研究員 (50719507)
吉住 朋晴  九州大学, 医学研究院, 准教授 (80363373)
池上 徹  九州大学, 大学病院, 講師 (80432938)
伊藤 心二  九州大学, 大学病院, 助教 (90382423)
Project Period (FY) 2018-04-01 – 2021-03-31
Keywordsエクソソーム / 癌関連線維芽細胞 / 肝細胞癌 / miRNA
Outline of Final Research Achievements

Hepatocellular carcinoma (HCC) is a common and deadly cancer. The prognosis of HCC is poor and is related to tumor progression. The malignant potential of HCC is regulated by the tumor microenvironment (TME). As cancer-associated fibroblasts (CAFs) help regulate tumor progression, understanding how they function in HCC could improve patient outcomes. The aim of this study was to determine whether specific microRNAs (miRNAs) in exosomes derived from CAFs might be involved in HCC progression.
Overall, our findings suggest that the loss of antitumoral miR-150-3p in CAFs-derived exosomes greatly promotes HCC progression. Exosomal miR-150-3p is a potential prognostic biomarker, and transferring miR-150-3p-loaded exosomes to HCC cells might become a novel therapeutic option.

Free Research Field

肝細胞癌の治療

Academic Significance and Societal Importance of the Research Achievements

これまで癌関連線維芽細胞(Cancer associated fibroblasts: CAFs)は、細胞間情報伝達を介して癌細胞の進展に影響し、Exosomeは様々な癌種で癌進展へ影響を及ぼしていることがわかっていた。今回初めて肝細胞癌微小環境における線維芽細胞由来exosomeの役割について検討したところ。肝癌微小環境においてCAFs-exosomeでは抗腫瘍効果のあるmiR-150-3p発現が低下し、癌細胞内でCDH2の発現が抑制解除されることで癌進展が促進している機序が判明した。今後予後の不良な肝細胞癌においてmiR-150-3pやCDH2を用いた革新的治療法へと繋がる可能性があった。

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Published: 2022-01-27  

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