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Identification of circulating stromal/cancer cell population detected in hepatocellular carcinoma.

Research Project

Project/Area Number 18H02792
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKanazawa University

Principal Investigator

Yamashita Taro  金沢大学, 附属病院, 准教授 (90377432)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords肝細胞癌 / 癌幹細胞 / 肝細胞がん / 癌間質細胞 / 肝癌幹細胞 / 肝癌間質細胞 / 循環癌間質細胞 / 1細胞トランスクリプトーム / バイオマーカー
Outline of Final Research Achievements

Hepatocellular carcinoma is the second leading cause of cancer death worldwide. In this study, we performed the immunohistochemistry and flow cytometer analysis to identify the cellular heterogeneity of tumor as well as stromal cells. We further performed the single cell transcriptome analysis using peripheral blood mononuclear cells of hepatocellular carcinoma patients. We identified that tumor stromal cells expressing PD1 or CCR6 as well as tumor cells expressing CCL20 were mostly detected at the periphery, not the center of the tumor. We further identified the circulating cell population specifically detected in hepatocellular carcinoma patients. Interestingly, these cell population contained both tumor cells and stromal cells potentially regulating immune system. This study provides important molecular basis of circulating cells potentially be utilized for the diagnosis and treatment of hepatocellular carcinoma.

Academic Significance and Societal Importance of the Research Achievements

肝癌は世界の悪性腫瘍による死因の第2位を占め、新たな診断治療法の開発が強く求められている。本研究では肝癌組織における間質細胞の多様性に注目、特に肝癌患者の血液中に存在する細胞集団に着目、健常人、慢性肝炎、肝硬変患者では存在せず、肝癌患者においてのみ出現する細胞集団を1細胞トランスクリプトーム解析により同定した。これらの細胞集団は肝癌の悪性度や免疫応答制御に関わる細胞集団である可能性がトランスクリプトームデータから示唆されている。今回の研究成果を応用することで新たな高悪性度肝癌の診断、治療の標的分子としての有用性を検討することが可能となり、大きな学術的、社会的意義を有する。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (8 results)

All 2021 2020 2018

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Liver cancer stem cells: Recent progress in basic and clinical research.2021

    • Author(s)
      Yamashita T, Kaneko S.
    • Journal Title

      Regen Ther.

      Volume: 17 Pages: 34-37

    • DOI

      10.1016/j.reth.2021.03.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum laminin γ2 monomer as a novel diagnostic and predictive biomarker for hepatocellular carcinoma.2021

    • Author(s)
      T Yamashita, N Koshikawa, T Shimakami, T Terashima, M Nakagawa, K Nio, R Horii, N Iida, K Kawaguchi, K Arai, Y Sakai, T Yamashita, E Mizukoshi, M Honda, A Kitao, S Kobayashi, S Takahara, Y Imai, K Yoshimura, T Murayama, Y Nakamoto, E Yoshida, T Yoshimura, M Seiki, S Kaneko.
    • Journal Title

      Hepatology

      Volume: - Issue: 2 Pages: 760-775

    • DOI

      10.1002/hep.31758

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inactivation of Transcriptional Repressor Capicua Confers Sorafenib Resistance in Human Hepatocellular Carcinoma2020

    • Author(s)
      Hashiba Tomomi、Yamashita Taro、et al
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 20 Issue: 2 Pages: 30039-4

    • DOI

      10.1016/j.jcmgh.2020.02.009

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The osteopontin-CD44 axis in hepatic cancer stem cells regulates IFN signaling and HCV replication.2018

    • Author(s)
      Shirasaki T, Honda M, Yamashita T, Nio K, Shimakami T, Shimizu R, Nakasyo S, Murai K, Shirasaki N, Okada H, Sakai Y, Sato T, Suzuki T, Yoshioka K, Kaneko S.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 13143-13143

    • DOI

      10.1038/s41598-018-31421-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] AFP,FOXM1をバイオマーカー、分子標的とした新規肝がん治療法の開発2020

    • Author(s)
      山下太郎、丹尾幸樹、金子周一
    • Organizer
      日本消化器病学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新たなリン酸化hTERT抗体による高悪性度肝がんの同定2020

    • Author(s)
      山下太郎、増富健吉、金子周一
    • Organizer
      日本肝臓学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 1.Dickkopf-1 is a new molecular target for the treatment of hepatocellular carcinoma2018

    • Author(s)
      Tsuyoshi Suda, Taro Yamashita, Shuichi Kaneko
    • Organizer
      AASLD Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hepatocellular Carcinoma and Pathogenesis2018

    • Author(s)
      Taro Yamashita
    • Organizer
      25th International Symposium on Hepatitis C Virus and Related Viruses
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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