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Establishment of a new preventive strategy based on the interaction of NK cells and prostate cancer stem cells

Research Project

Project/Area Number 21K11638
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionToyo University

Principal Investigator

Yano Tomohiro  東洋大学, 健康スポーツ科学部, 教授 (50239828)

Co-Investigator(Kenkyū-buntansha) 加藤 和則  東洋大学, 理工学部, 教授 (60233780)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords前立腺がん幹細胞 / NK細胞 / 殺細胞効果 / TRAIL/DR5 / NKG2D / MICA/MICB / 免疫チェックポイント / STAT3 / TRAIL/DR5経路 / 前立腺がん予防法
Outline of Research at the Start

前立腺がん幹細胞を標的とした根本的な前立腺がん予防法を構築するために、NK細胞が選択的にがん幹細胞を攻撃できる能力に着目し、この能力を増強する機能性食素材をNK細胞と前立腺がん幹細胞の共培養系を用いて、スクリーニングする。そして、スクリーニングされた機能性食素材を摂取したヒトから分離したNK細胞を用いて、前立腺がん幹細胞に対する殺細胞効果を検討し、最終的に、このスクリーニングされた機能性食素材を用いたNK細胞による前立腺がん幹細胞を標的とした前立腺がん予防法構築の可能性を検証する。

Outline of Final Research Achievements

Focusing on the phenotype that NK cells selectively recognize and eliminate cancer stem cells, we investigated the possibility of developing prevention and treatment methods for prostate cancer, based on this phenotype in NK cells. In study on prostate cancer prevention approach, NK cells specifically activated the TRAIL/DR5 pathway against hormone-dependent prostate cancer stem-like cells, and in study on treatment approach, hormone-independent prostate cancer stem-like cells NK cells specifically activated the NKG2D/MICA/MICB pathway, which is one of the activation receptor pathways, for prostate cancer stem-like cells (CRPC), respectively. These results strongly suggested that NK cells could specifically eliminated hormone-dependent and independent prostate cancer stem-like cells. However, it was shown that immune checkpoints are activated in CRPC cells, which are more malignant, and the cell-killing effect of NK cells is weakened.

Academic Significance and Societal Importance of the Research Achievements

現在罹患者数が増加している前立腺がんはその予防法と並び、治療再発後のホルモン非依存性(CRPC)の前立腺がんの治療法の開発が急務である。本研究では前立腺がん幹細胞を標的としてNK細胞が特異的にホルモン依存性及びホルモン非依存性前立腺がん幹細胞を除去する可能性を示し、NK細胞が前立腺がん幹細胞を特異的に除去できるという性質に基づいた、新たな前立腺がん予防・治療法の可能性が示され、今後NK細胞のこの性質を強化する方法論を構築することが、新たな前立腺がん予防治療法の構築につながると推測される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 2021 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] α-Tocotrienol and Redox-Silent Analogs of Vitamin E Enhances Bortezomib Sensitivity in Solid Cancer Cells through Modulation of NFE2L12023

    • Author(s)
      Ishii K, Hido M, Sakamura M, Virgona N, Yano T.
    • Journal Title

      Int J Mol Sci

      Volume: 24 Issue: 11 Pages: 9382-9382

    • DOI

      10.3390/ijms24119382

    • Related Report
      2023 Annual Research Report
  • [Journal Article] CHEMORESISTANCE RELATED TO HYPOXIA ADAPTATION IN MESOTHELIOMA CELLS FROM TUMOR SPHEROIDS2022

    • Author(s)
      Endoh D, Ishii K, Kohno K, Virgona N, Miyakoshi Y, Yano T, Ishida T.
    • Journal Title

      Exp Oncol

      Volume: 44 Issue: 2 Pages: 121-125

    • DOI

      10.32471/exp-oncology.2312-8852.vol-44-no-2.18045

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NK Cells Can Preferentially Target Prostate Cancer Stem-like Cells via the TRAIL/DR5 Signaling Pathway2021

    • Author(s)
      Seki T, Shimizu Y, Ishii K, Takahama Y, Kato K, Yano T.
    • Journal Title

      Biomolecules

      Volume: 11 Issue: 11 Pages: 1702-1702

    • DOI

      10.3390/biom11111702

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Alpha-Connexin Carboxyl-Terminal Peptide (aCT1) and Bowman-Birk Protease Inhibitor (BBI) on Canine Oral Mucosal Melanoma (OMM) Cells.2021

    • Author(s)
      Sato A, da Fonseca IIM, Nagamine MK, de Toledo GF, Olio R, Hernandez-Blazquez FJ, Yano T, Yeh ES, Dagli MLZ.
    • Journal Title

      Front Vet Sci.

      Volume: 8 Pages: 670451-670451

    • DOI

      10.3389/fvets.2021.670451

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 去勢抵抗性前立腺がん、すい臓がんにおけるトコトリエノールのNRF3阻害効果と補完代替成分としての可能性2023

    • Author(s)
      石井亨太、矢野友啓
    • Organizer
      第21回日本機能性食品医用学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヒト前立腺がん細胞におけるδートコトリエノールによるHIF阻害効果の検討2023

    • Author(s)
      田内優乃、石井亨太、河野翔、矢野友啓
    • Organizer
      第21回日本機能性食品医用学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ナチュラルキラー(NK)細胞は去勢抵抗性前立腺がん幹細胞を優先的に傷害する2022

    • Author(s)
      関大河、矢野友啓
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] NK Cells Preferentially Target Prostate Cancer Stem-like Cells2021

    • Author(s)
      Seki T, Yano T
    • Organizer
      Sydney Cancer Conference 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Death receptor pathway in NK cells regulate prostate cancer stem cells2021

    • Author(s)
      関大河、矢野友啓
    • Organizer
      第80回日本癌学会総会
    • Related Report
      2021 Research-status Report
  • [Remarks]

    • URL

      https://www.toyo.ac.jp/academics/faculty/hcs/professor1/nutrition/yano/

    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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