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The novel anti-cancer therapy by suppression of cancer microenvironment that promotes hepatocarcinogenesis

Research Project

Project/Area Number 17K16562
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

MOTOMURA takashi  九州大学, 医学研究院, 共同研究員 (50719507)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肝癌微小環境 / 癌関連マクロファージ / 癌関連線維芽細胞 / 肝癌 / CAF / TAM / NK細胞 / マクロファージ / 線維芽細胞 / 微小環境 / 腫瘍関連マクロファージ
Outline of Final Research Achievements

Fibroblast was isolated from cancer- and non-cancerous tissue of human resected liver, and defined as cancer-associated fibroblast(CAF) and normal fibroblast(NF), respectively. Hepatoma cell line when co-cultured with exosome derived from CAF showed higher invasion. In the exosome from CAF, miR150-3p was significantly lower compared with NF. Over expression of miR150-3p showed higher invasive capacity of hepatoma cell line. Using the database, the negative target gene of miR150-3p was identified: CDH2. Knockdown of CDH2 in hepatoma cell line showed decreased invasive capacity. Immunohistochemical stain was done. Among patients who underwent hepatectomy for hepatocellular carcinoma, overall- and recurrence free survival rate was significantly worse in high CDH2 group.

Academic Significance and Societal Importance of the Research Achievements

肝癌の再発には炎症性癌微小環境が大きく関わっていることが明らかになっている。また肝・脾におけるマクロファージのphenotypeの相違が肝線維化に関わっているとも考えられている。これら組織間のマクロファージや肝線維芽細胞、肝細胞との関係と各種サイトカインを詳細に検討することで、成因を超えた肝線維化と肝発癌の抑制につながる可能性が高く、かつそうした創薬はこれまでになく我が国独創的である。さらに癌微小環境は各癌腫でも注目されており、今回の検討が臓器を超えた普遍的な癌治療に結びつく可能性も秘めている。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (1 results)

All 2019

All Presentation (1 results)

  • [Presentation] 肝癌微小環境における癌関連線維芽細胞由来のエクソソームの意義2019

    • Author(s)
      湯川 恭平
    • Organizer
      第119回 日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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