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Characterization of islet-derived pancreatic cancer

Research Project

Project/Area Number 22K19421
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionGunma University

Principal Investigator

FUJITANI Yoshio  群馬大学, 生体調節研究所, 教授 (30433783)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords膵島 / PP細胞 / 膵がん / 内分泌細胞 / 膵癌 / islet / pancreatic cancer / PDAC / PP cell
Outline of Research at the Start

最近の研究の進歩により、早期癌の治療成績は確実に改善してきた。そのなかにあって膵臓癌の5年生存率は10%を切る程度であり、新たな診断・治療法の開発が急務である。現在、膵癌は膵腺房細胞あるいは導管細胞から発生すると考えられている。本研究では我々が開発した動物モデルを用いて、膵ランゲルハンス島に存在する膵内分泌細胞から膵臓癌が発生する仕組みを研究する。本研究は、膵癌発生についての新知見をもたらし、これまでにない診断・治療法に繋がる可能性がある。

Outline of Final Research Achievements

The five-year survival rate for pancreatic cancer is extremely low compared to other types of cancer such as stomach cancer. This is due to the difficulty in diagnosing the disease at an early stage. When the disease is diagnosed, it is often in an advanced stage, making the development of early diagnosis techniques and treatment methods an urgent issue. The origin of pancreatic cancer has conventionally been thought to be exocrine cells, which are mainly responsible for the production of digestive enzymes. In this study, we focused on PP cells, one of the endocrine cells in the pancreatic islets. Using genetically-modified mice, the researchers found that activation of oncogenes in these cells resulted in the extremely early development of pancreatic cancer. It is expected that the detailed characteristics of pancreatic cancer that develops from PP cells will be clarified in the future, leading to the development of therapeutic methods.

Academic Significance and Societal Importance of the Research Achievements

膵臓がんの5年生存率は、胃がんなど他のがん種に比べて極端に低い。早期の診断が難しいのが原因で、診断されたときは病気が進んでいることが多く、早期診断技術と治療法の開発が喫緊の課題となっている。膵臓がんの起源は従来、主に消化酵素の生成を担う外分泌細胞と考えられてきた。本研究では膵島内の内分泌細胞の一つ、PP細胞に着目。遺伝子組み換えマウスを使い、この細胞において、がん遺伝子を活性化させると膵臓がんが極めて早期に発症する結果が得られた。今後、PP細胞から発症する膵臓がんの詳しい特徴が明らかにされることにより、治療法の開発につながることが期待される。

Report

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

    (21 results)

All 2024 2023 2022 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (14 results) (of which Invited: 7 results) Remarks (2 results)

  • [Journal Article] Identification of Ppy-lineage cells as a novel origin of pancreatic ductal adenocarcinoma.2024

    • Author(s)
      Pereye OB, Nakagawa Y, Sato T, Fukunaka A, Aoyama S, Nishida Y, Mizutani W, Kobayashi Y, Sato T, Fukunaka A, Aoyama S, Nishida Y, Mizutani W, Kobayashi N, Morishita
    • Journal Title

      Journal of Pathology

      Volume: in press

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel-time resolved reporter mouse reveals spatial and transcriptional heterogeneity during alpha cell differentiation2023

    • Author(s)
      Himuro M, Wakabayashi Y, Taguchi T, Katahira T, Suzuki L, Iida H, Ogihara T, Nishida Y, Sasaki S, Lynn FC, Hiraoka Y, Oshima S, Okamoto R, Fujitani Y, Watada H, Miyatsuka T
    • Journal Title

      Diabetologia

      Volume: 67 Issue: 1 Pages: 156-169

    • DOI

      10.1007/s00125-023-06028-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Zinc and iron dynamics in human islet amyloid polypeptide-induced diabetes mouse model2023

    • Author(s)
      Fukunaka Ayako、Shimura Mari、Ichinose Takayuki、Pereye Ofejiro B.、Nakagawa Yuko、Tamura Yasuko、Mizutani Wakana、Inoue Ryota、Inoue Takato、Tanaka Yuto、Sato Takashi、Saitoh Tatsuya、Fukada Toshiyuki、Nishida Yuya、Miyatsuka Takeshi、Shirakawa Jun、Watada Hirotaka、Matsuyama Satoshi、Fujitani Yoshio
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 3484-3484

    • DOI

      10.1038/s41598-023-30498-y

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of an enzyme-linked immunosorbent assay for mouse pancreatic polypeptide clarifies the regulatory mechanism of its secretion from pancreatic γ cells2022

    • Author(s)
      Saito Daisuke、Nakagawa Yuko、Sato Takashi、Fukunaka Ayako、Pereye Ofejiro Blessing、Maruyama Nobuhiro、Watada Hirotaka、Fujitani Yoshio
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 8 Pages: e0269958-e0269958

    • DOI

      10.1371/journal.pone.0269958

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cumulative autophagy insufficiency in mice leads to progression of β-cell failure2022

    • Author(s)
      Suzuki L, Miyatsuka T, Himuro M, Wakabayashi Y, Osonoi S, Miura M, Katahira T, Fujitani Y, Iida H, Mizukami H, Nishida Y, Watada H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 611 Pages: 38-45

    • DOI

      10.1016/j.bbrc.2022.04.040

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵β細胞の機能的多様性2023

    • Author(s)
      藤谷与士夫
    • Organizer
      第57回糖尿病学の進歩 (オンデマンド配信)
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Invited
  • [Presentation] PP細胞から切り拓く膵島研究の新展開2023

    • Author(s)
      藤谷与士夫
    • Organizer
      第66回日本糖尿病学会年次学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] New islet research pioneered through PP cells2023

    • Author(s)
      藤谷与士夫
    • Organizer
      国際糖尿病連合西太平洋地区会議2023
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 内分泌細胞である膵PP細胞から膵腺癌を発症する新たな発癌モデルマウスの開発とその意義2023

    • Author(s)
      藤谷与士夫
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] PPY発現細胞は膵癌の新たな起源細胞となりうる2023

    • Author(s)
      藤谷与士夫
    • Organizer
      第37回日本糖尿病・肥満動物学会年次学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 膵内分泌細胞に由来する膵管腺癌モデルの発症機構の解析2023

    • Author(s)
      中川祐子, Ofejiro B. Pereye, 佐藤隆史, 福中彩子, 青山周平, 西田友哉, 森下揚平, 川端麗香, 綿田裕孝, 水上浩哉, 福田晃久, 藤谷与士夫
    • Organizer
      第37回日本糖尿病・肥満動物学会年次学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Genetically induced immortalization of Ppy-expressing cells results in pancreatic ductal adenocarcinoma2023

    • Author(s)
      Ofejiro B. Pereye, Takashi Sato, Yuko Nakagawa, Ayako Fukunaka, Akihisa Fukuda, Hiroki Mizukami and Yoshio Fujitani
    • Organizer
      第36回日本糖尿病肥満動物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Genetically induced immortalization of Ppy-expressing cells results in pancreatic ductal adenocarcinoma2023

    • Author(s)
      Ofejiro B. Pereye, 佐藤隆史, 中川祐子,福中彩子, 青山周平, 西田友哉, 綿田裕孝, 福田晃久, 水上浩哉, 藤谷与士夫
    • Organizer
      日本生理学会 第100回記念大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Ppy遺伝子の活性化が膵β細胞の機能的多様性を規定する2022

    • Author(s)
      藤谷与士夫
    • Organizer
      第65回日本糖尿病学会年次学術集会 シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] PP細胞研究から解き明かす膵β細胞の多様性2022

    • Author(s)
      藤谷与士夫
    • Organizer
      第95回日本内分泌学会学術総会 シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] A novel Islet-derived mouse pancreatic ductal adenocarcinoma model2022

    • Author(s)
      Ofejiro B. Pereye, 佐藤隆史, 中川祐子, 福中彩子, 藤谷与士夫
    • Organizer
      第35回日本糖尿病肥満動物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Genetically induced immortalization of Ppy-expressing cells results in malignant transformation2022

    • Author(s)
      Ofejiro B. Pereye, 佐藤隆史, 中川祐子, 福中彩子, 藤谷与士夫
    • Organizer
      第95回日本内分泌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Genetically induced immortalization of Ppy-expressing cells results in Pancreatic Ductal Adenocarcinoma2022

    • Author(s)
      Ofejiro B. Pereye, 佐藤隆史, 中川祐子,福中彩子, 青山周平, 西田友哉, 綿田裕孝, 福田晃久, 水上浩哉, 藤谷与士夫
    • Organizer
      25th Diabetes Research Forum
    • Related Report
      2022 Research-status Report
  • [Presentation] Genetically induced immortalization of Ppy-expressing cells result in Pancreatic Ductal Adenocarcinoma2022

    • Author(s)
      Ofejiro B. Pereye, Takashi Sato, Yuko Nakagawa, Ayako Fukunaka, Shuhei Aoyama, Yuya Nishida, Hirotaka Watada, Akihisa Fukuda, Hiroki Mizukami and Yoshio Fujitani
    • Organizer
      The 8th IMCR Symposium on Endocrine and Metabolism
    • Related Report
      2022 Research-status Report
  • [Remarks] 生体調節研究所 分子糖代謝制御分野 藤谷研究室

    • URL

      https://tou-taisha.imcr.gunma-u.ac.jp/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 生体調節研究所 分子糖代謝制御分野 藤谷研究室

    • URL

      https://tou-taisha.imcr.gunma-u.ac.jp/

    • Related Report
      2022 Research-status Report

URL: 

Published: 2022-07-05   Modified: 2025-01-30  

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