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Establishing a 3D model of fibrosis in pancreatic cancer and analysis of interaction between tumor cells and stellate cells

Research Project

Project/Area Number 18H02797
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Kano Mitsunobu  岡山大学, ヘルスシステム統合科学学域, 教授 (80447383)

Co-Investigator(Kenkyū-buntansha) 正宗 淳  東北大学, 医学系研究科, 教授 (90312579)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywords膵がん / 間質 / 線維化 / 三次元培養 / 三次元培養法 / 細胞外基質 / 線維芽細胞 / 腫瘍微小環境 / 薬物送達 / 膵星細胞 / 膵臓がん / 膵臓星状細胞 / 膵癌 / 膵臓星状細胞(PSC) / 立体培養
Outline of Final Research Achievements

Our hypothesis is that fibrosis within tumour tissue is an important determinant of clinical drug efficacy. We worked on the verification of this hypothesis through three-dimensional culture of its constituent cells, pancreatic stellate cells (PSCs). Specifically, the thickness of fibrotic tissue was measured in human cases and three-dimensional cultured tissue with equivalent thickness was created. The ECM proteins involved in fibrosis were visualised and analysed in the fibrotic tissue model, and differences between pancreatic cancer-derived PSCs and normal fibroblasts were revealed. We developed a three-dimensional co-culture model between PSCs and pancreatic cancer cells, and succeeded in creating three-dimensional co-cultured tissue that reproduced the range of tumour tissue occupancy rates observed clinically. Consequently, we were able to reproduce and analyse mechanism of the acquisition of PSC trait abnormalities by co-culturing with pancreatic cancer cells.

Academic Significance and Societal Importance of the Research Achievements

膵がんは我が国のがん死亡の原因4位である。特にその8割以上を占める膵管腺癌は難治である。膵がんの五年生存率は依然として1割前後であり、数十年来、本質的な改善がない。特に手術適応のない進行性膵がんでは、抗腫瘍剤が主な治療法であるが不応例が多い。膵がんで薬物療法の奏功程度が低い原因は、腫瘍細胞そのものの薬剤感受性や抵抗性を含めて様々ありうるなか、本研究では顕著な腫瘍組織内の線維化が臨床薬効の重要な規定因子であるという仮説の検証を進めた。膵がんを含む線維化を伴う疾患の新規治療法開拓への礎となることが期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(29 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (8 results) (of which Open Access: 5 results,  Peer Reviewed: 5 results) Presentation (18 results) (of which Int'l Joint Research: 7 results,  Invited: 12 results) Book (1 results) Remarks (2 results)

  • [Journal Article] がん微小環境における線維化とナノ DDS2021

    • Author(s)
      田中啓祥、狩野光伸
    • Journal Title

      Drug Delivery System

      Volume: 36 Pages: 232-240

    • DOI

      10.2745/dds.36.232

    • Related Report
      2021 Annual Research Report
    • Open Access
  • [Journal Article] がん微小環境を取り巻く諸科学2021

    • Author(s)
      狩野光伸
    • Journal Title

      Drug Delivery System

      Volume: 36 Pages: 229-229

    • DOI

      10.2745/dds.36.229

    • Related Report
      2021 Annual Research Report
    • Open Access
  • [Journal Article] Heterotypic 3D pancreatic cancer model with tunable proportion of fibrotic elements2020

    • Author(s)
      Tanaka Hiroyoshi Y.、Kurihara Tsuyoshi、Nakazawa Takuya、Matsusaki Michiya、Masamune Atsushi、Kano Mitsunobu R.
    • Journal Title

      Biomaterials

      Volume: 251 Pages: 120077~120077

    • DOI

      10.1016/j.biomaterials.2020.120077

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selection of Tumor models2020

    • Author(s)
      Takashima Hiroki、Koga Yoshikatsu、Tsumura Ryo、Fuchigami Hirobumi、Matsumura Yasuhiro、Yasunaga Masahiro、Tanaka Hiroyoshi Y.、Kurihara Tsuyoshi、Kano Mitsunobu R.
    • Journal Title

      Drug Delivery System

      Volume: 35 Pages: 443~447

    • DOI

      10.2745/dds.35.443

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers2019

    • Author(s)
      Watanabe S, Hayashi K, Toh K, Kim HJ, Liu X, Chaya H, Fukushima S, Katsushima K, Kondo Y, Uchida S, Ogura S, Nomoto T, Takemoto H, Cabral H, Kinoh H, Tanaka HY, Kano MR, Matsumoto Y, Fukuhara H, Uchida S, Nangaku M, Osada K, Nishiyama N, Miyata K, Kataoka K
    • Journal Title

      Nature Communications

      Volume: 10 Pages: 1-13

    • DOI

      10.1038/s41467-019-09856-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreatic stellate cells derived from human pancreatic cancer demonstrate aberrant SPARC-dependent ECM remodeling in 3D engineered fibrotic tissue of clinically relevant thickness2019

    • Author(s)
      Tanaka Hiroyoshi Y.、Kitahara Kentaro、Sasaki Naoki、Nakao Natsumi、Sato Kae、Narita Hirokazu、Shimoda Hiroshi、Matsusaki Michiya、Nishihara Hiroshi、Masamune Atsushi、Kano Mitsunobu R.
    • Journal Title

      Biomaterials

      Volume: 192 Pages: 355~367

    • DOI

      10.1016/j.biomaterials.2018.11.023

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment2018

    • Author(s)
      Tanaka Hiroyoshi Y.、Kano Mitsunobu R.
    • Journal Title

      Cancer Science

      Volume: 109 Pages: 2085~2092

    • DOI

      10.1111/cas.13630

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In?vitro 3D blood/lymph-vascularized human stromal tissues for preclinical assays of cancer metastasis2018

    • Author(s)
      Nishiguchi Akihiro、Matsusaki Michiya、Kano Mitsunobu R.、Nishihara Hiroshi、Okano Daisuke、Asano Yoshiya、Shimoda Hiroshi、Kishimoto Satoko、Iwai Soichi、Akashi Mitsuru
    • Journal Title

      Biomaterials

      Volume: 179 Pages: 144~155

    • DOI

      10.1016/j.biomaterials.2018.06.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] がん微小環境とイメージング2022

    • Author(s)
      田中啓祥、狩野光伸
    • Organizer
      MRIコラボ・ワークショップ2022
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 三次元培養法による膵がん線維化組織のモデル化および筋線維芽細胞分化機序の解析2022

    • Author(s)
      中澤拓也、田中啓祥、狩野光伸
    • Organizer
      日本薬学会第142回年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 線維化量を制御可能なヒト膵がん微小環境の三次元培養モデルの確立・解析とナノDDS研究への応用2021

    • Author(s)
      田中啓祥、狩野光伸
    • Organizer
      第37回日本DDS学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Heterotypic 3D Cell Culture Model Of The Pancreatic Cancer Tumor Microenvironment With A Tunable Proportion Of Fibrotic Elements2021

    • Author(s)
      Hiroyoshi Y. Tanaka, Mitsunobu R. Kano
    • Organizer
      EACR Goodbye Flat Biology: Next Generation Cancer Models
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵臓がん線維化組織の3D培養モデルを利用したナノ薬剤送達効率の解析2020

    • Author(s)
      田中啓祥,狩野光伸
    • Organizer
      第36回日本DDS学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Heterotypic 3D Culture Model of the Pancreatic Cancer Microenvironment with a Tunable Proportion of Fibrotic Elements2020

    • Author(s)
      田中啓祥,正宗 淳,狩野光伸
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Why pancreatic cancer is difficult to treat: analyzing the characteristics of the disease tissue2020

    • Author(s)
      Mitsunobu R Kano
    • Organizer
      4th International Pharma Conference "Global Challenges and Pharmaceutical Impacts"
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Scientific thinking and the real world-thoughts from medicine and SDGs2020

    • Author(s)
      Mitsunobu R Kano
    • Organizer
      Challenges facing humanity at the age of COVID-19 and beyond: Women in Science Without Borders
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Thoughts on the use of Information Science: Importance of QUESTIONS2019

    • Author(s)
      Mitsunobu R Kano
    • Organizer
      "lndia-Japan Collaborative Workshop on Health Research" jointly organized by AMED and ICMR-DST
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Thoughts on STI to achieve the SDGs2019

    • Author(s)
      Mitsunobu R Kano
    • Organizer
      Tsukuba Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 膵臓がんにおいてナノ薬剤送達の障壁となる線維化組織の立体培養法によるモデル化および解析2019

    • Author(s)
      田中啓祥, 狩野光伸
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Pancreatic stellate cells from human pancreatic cancer show aberrant ECM remodeling in 3D engineered fibrotic tissue2019

    • Author(s)
      田中啓祥, 狩野光伸
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 立体培養法による組織微小環境モデルの開発および疾患研究への応用2019

    • Author(s)
      田中啓祥, 狩野光伸
    • Organizer
      日本化学会第100春季年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 大学はSDGs達成にどのようにかかわれるか2019

    • Author(s)
      狩野光伸
    • Organizer
      第71回生物工学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 世界と地域に新たな価値を創造しつづけるSDGs推進研究大学2019

    • Author(s)
      狩野光伸
    • Organizer
      日経SDGsフォーラム 特別シンポジウム 社会的共通資本としての医療
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 難治の病気に科学技術で立ち向かうには2019

    • Author(s)
      狩野光伸
    • Organizer
      外務省科学技術外交セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Answering questions from the real world -from medicine to the SDGs-2019

    • Author(s)
      Mitsunobu R Kano
    • Organizer
      3rd International Conference of Women in Science without Borders (WISWB), Cairo, Egypt
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 膵がんにおける組織構築の特徴とナノ薬剤の活用法を考える2018

    • Author(s)
      狩野光伸・田中啓祥
    • Organizer
      日本DDS学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] Stromal barriers within the tumor microenvironment and obstacles to nanomedicine (Cancer Drug Delivery Systems based on the Tumor Microenvironment, Chapter 4)2019

    • Author(s)
      Tanaka HY, Kano MR
    • Total Pages
      33
    • Publisher
      Springer Nature
    • ISBN
      978-4-431-56878-0
    • Related Report
      2019 Annual Research Report
  • [Remarks] 岡山大学SDGs取組事例

    • URL

      https://sdgs.okayama-u.ac.jp/efforts/detail.php?seq=58

    • Related Report
      2018 Annual Research Report
  • [Remarks] 研究室紹介

    • URL

      https://sites.google.com/view/kanolab-ph-biol-gsisehs-ou/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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