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Elucidation and control of pancreatic cancer-stroma interaction by artificial cancer tissue construction

Research Project

Project/Area Number 19H03718
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionNational Cancer Center Japan (2020-2021)
The University of Tokyo (2019)

Principal Investigator

Sekine Keisuke  国立研究開発法人国立がん研究センター, 研究所, ユニット長 (00323569)

Co-Investigator(Kenkyū-buntansha) 谷口 英樹  東京大学, 医科学研究所, 教授 (70292555)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywordsオルガノイド / 癌 / 膵癌
Outline of Research at the Start

申請者らは、これまでに間質を伴う正常組織の人為的再構成法を基盤とし、日本人膵癌患者より分離したプライマリ膵癌細胞を用いて、膵癌微小環境を再現可能なヒトプライマリ膵癌オルガノイド作製法を開発した。ヒトプライマリ膵癌オルガノイドは高い抗癌剤耐性を示すことから、膵癌患者の高い治療抵抗性を再現するための手法を確立したといえる。
本研究では、膵癌の進展に必須と考えられる膵癌細胞と間質の相互作用を、申請者らが開発したヒトプライマリ膵癌オルガノイドを用いた人為的な癌間質の操作とその特性解析、独自のシングルセルレベルでの解析手法により明らかにし、膵癌制圧のための膵癌細胞-間質相互作用の制御を試みる。

Outline of Final Research Achievements

In this study, we performed in vivo spatial omics analysis for the purpose of clarifying pancreatic cancer cell-stromal interactions. Furthermore, primary cells were established from clinical specimens, and a single-cell level comprehensive gene expression analysis was performed on the established primary cells. By conducting informatics analysis that integrates these data, we carried out ligand-receptor analysis and intracellular signal network analysis related to transcription factor networks and cell-cell interactions. We succeeded in identifying a possible transcription factor network and candidate molecules for multiple pancreatic cancer cell-interstitial interactions.

Academic Significance and Societal Importance of the Research Achievements

膵癌は極めて予後の悪い難治癌であり、本邦では肝癌を抜いて第4位となっており、2030年までには第2位となるとの予測もあるなど、予後の改善に向けた開発が社会的要求が高いといえる。本研究では膵癌の進展に必須と考えられる膵癌細胞と間質の間におこる相互作用に関与すると考えられる転写因子ネットワークの同定と複数の膵癌細胞-間質相互作用の候補分子の同定に成功した。今後これらの分子を標的とした機能解析と創薬開発により、膵癌の予後改善に貢献する可能性が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (26 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 9 results) Book (1 results) Patent(Industrial Property Rights) (7 results) (of which Overseas: 4 results)

  • [Int'l Joint Research] Technical University of Munich/Max Planck Inst for Evo Anthropol/Ulm University Hospital(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ETH Zurich/Inst Mol Clin Ophthalmology Basel(スイス)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development2022

    • Author(s)
      Krumm J, Sekine K, Samaras P, Brazovskaja A, Breunig M, Yasui R, Kleger A, Taniguchi H, Wilhelm M, Treutlein B, Camp JG, Kuster B
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 13 Pages: 110604-110604

    • DOI

      10.1016/j.celrep.2022.110604

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Robust parameter design of human induced pluripotent stem cell differentiation protocols defines lineage-specific induction of anterior-posterior gut tube endodermal cells.2021

    • Author(s)
      Yasui R, Sekine K, Yamaguchi K, Furukawa Y, Taniguchi H
    • Journal Title

      Stem Cells

      Volume: 39 Issue: 4 Pages: 429-442

    • DOI

      10.1002/stem.3326

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clever Experimental Designs: Shortcuts for Better iPSC Differentiation.2021

    • Author(s)
      Yasui R, Sekine K, Taniguchi H.
    • Journal Title

      Cells

      Volume: 10 Issue: 12 Pages: 3540-3540

    • DOI

      10.3390/cells10123540

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Organoid and Supporting Technologies for Cancer and Toxicological Research2021

    • Author(s)
      Sekine K
    • Journal Title

      Frontiers in Genetics

      Volume: 12 Pages: 759366-759366

    • DOI

      10.3389/fgene.2021.759366

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of PDX‐derived salivary adenoid cystic carcinoma cell lines using organoid culture method2020

    • Author(s)
      Takada Kentaro、Aizawa Yoshihiro、Sano Daisuke、Okuda Ryo、Sekine Keisuke、Ueno Yasuharu、Yamanaka Shoji、Aoyama Jun、Sato Kaname、Kuwahara Tatsu、Hatano Takashi、Takahashi Hideaki、Arai Yasuhiro、Nishimura Goshi、Taniguchi Hideki、Oridate Nobuhiko
    • Journal Title

      International Journal of Cancer

      Volume: 148 Issue: 1 Pages: 193-202

    • DOI

      10.1002/ijc.33315

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media2020

    • Author(s)
      Sekine K, Ogawa S, Tsuzuki S, Kobayashi T, Ikeda K, Nakanishi N, Takeuchi K, Kanai E, Otake Y, Okamoto S, Kobayashi T, Takebe T, Taniguchi H.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 17937-17937

    • DOI

      10.1038/s41598-020-73908-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Robust detection of undifferentiated iPSC among differentiated cells.2020

    • Author(s)
      Sekine K, Tsuzuki S, Yasui R, Kobayashi T, Ikeda K, Hamada Y, Kanai E, Camp JG, Treutlein B, Ueno Y, Okamoto S, Taniguchi H.
    • Journal Title

      Sci Rep.

      Volume: 10(1) Issue: 1 Pages: 10293-10293

    • DOI

      10.1038/s41598-020-66845-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Recapitulating pancreatic cancer ecosystems by multicellular cancer organoid cultures.2022

    • Author(s)
      関根圭輔
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] がんエコシステム解明に向けた患者由来癌モデルの構築2021

    • Author(s)
      関根圭輔
    • Organizer
      講演会:新しい治療法の開発を目指す患者由来がんモデル
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] がんオルガノイドを用いたゲノム編集とその可能性2021

    • Author(s)
      関根圭輔
    • Organizer
      第11回がん新薬開発合同シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Multicellular cancer organoid recapitulating cancer ecosystem using patient-derived pancreatic cancer cells2021

    • Author(s)
      関根圭輔
    • Organizer
      第44回 日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Elucidation and control of cancer ecosystem using artificial cancer tissue.2020

    • Author(s)
      Keisuke Sekine
    • Organizer
      The 79th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Generation of human liver using iPS cells for regenerative therapies2019

    • Author(s)
      Keisuke Sekine
    • Organizer
      American Association for the Study of Liver Diseases(AASLD)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Generation of functional human liver from pluripotent stem cell.2019

    • Author(s)
      Keisuke Sekine
    • Organizer
      26th East Asia Joint Symposium on Biomedical Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Multicellular cancer organoid cultures for recapitulating cancer ecosystems2019

    • Author(s)
      Keisuke Sekine
    • Organizer
      The 78th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Recapitulating pancreatic cancer ecosystems by multicellular cancer organoid cultures based on patient-derived cancer cells2019

    • Author(s)
      関根圭輔
    • Organizer
      患者由来がんモデル
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Book] 患者由来がんモデルを用いたがん研究実践ガイド、佐々木博己/編2019

    • Author(s)
      関根圭輔
    • Total Pages
      294
    • Publisher
      羊土社
    • ISBN
      9784758122429
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 未分化細胞の分化抵抗性評価法2020

    • Inventor(s)
      関根圭輔、谷口英樹
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 多能性幹細胞からの立体臓器の構築2020

    • Inventor(s)
      谷口英樹、武部貴則、関根圭輔
    • Industrial Property Rights Holder
      谷口英樹、武部貴則、関根圭輔
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-557347
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 再構成癌組織を用いた薬剤評価方法2019

    • Inventor(s)
      関根圭輔、谷口英樹、上野康晴、奥田諒、森永聡一郎、宮城洋平
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹、上野康晴、奥田諒、森永聡一郎、宮城洋平
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 上皮間葉転換関連分子を用いた癌評価法2019

    • Inventor(s)
      関根圭輔、谷口英樹、上野康晴、奥田諒、森永聡一郎、宮城洋平
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹、上野康晴、奥田諒、森永聡一郎、宮城洋平
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 未分化細胞検出法2019

    • Inventor(s)
      関根圭輔、谷口英樹、安居良太
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹、安居良太
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-207002
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 未分化マーカー遺伝子高感度検出法2019

    • Inventor(s)
      関根圭輔、谷口英樹、安居良太、松井貴香
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹、安居良太、松井貴香
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-207004
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 未分化細胞検出法2019

    • Inventor(s)
      関根圭輔、谷口英樹
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas

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Published: 2019-04-18   Modified: 2023-01-30  

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