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iCAF: Cancer associated fibroblast derived from iPS cells and its surface glycan as a target of cancer therapy.

Research Project

Project/Area Number 15H04924
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionUniversity of Tsukuba

Principal Investigator

Tatsuya ODA  筑波大学, 医学医療系, 教授 (20282353)

Co-Investigator(Kenkyū-buntansha) 木田 泰之  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (20396526)
舘野 浩章  国立研究開発法人産業技術総合研究所, 生命工学領域, 上級主任研究員 (30450670)
Co-Investigator(Renkei-kenkyūsha) HIRABAYASHI Jun  国立研究開発法人・産業技術総合研究所, 幹細胞工学研究センター・糖鎖レクチン工学研究チーム, 主席研究員・研究チーム長 (40156691)
ISHII Genichirou  独立行政法人・国立がん研究センター, 臨床腫瘍病理部, 室長 (00270869)
OHKOHCHI Nobuhiro  筑波大学, 医学医療系, 教授 (40213673)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords膵癌 / 癌ー間質相互作用 / CAF (がん関連線維芽細胞) / 糖鎖 / レクチン / ドラッグデリバリー / がん関連線維芽細胞:CAF / がんー間質相互作用 / 膵臓外科学 / CAF(癌関連線維芽細胞) / 癌 / 癌-間質相互作用 / トキシン / ラッグデリバリー / 癌—間質相互作用
Outline of Final Research Achievements

We comprehensively analyzed glyacan expression of clinical pancreatic cancer stem cell-like cell line (CSCL-1), and identified that H type 3 sugar chain was specifically expressed, and that rBC2 lectin binds to it. In addition, we have studied application of rBC2 lectin as a therapeutic carrier targeting direct cancer stem cells.
In addition, when mesenchymal stem cells are co-cultured with CSCL-1 and transplanted subcutaneously into mice, CAF boosted tumor growth. When the CAF was isolated as the first generation (F1), F2 the tumor growth capacity gradually weakened as the generation progress (i.e. F0, F1, F2 ), while the CAF marker showed a tendency to become higher.

Academic Significance and Societal Importance of the Research Achievements

癌関連線維芽細胞(CAF)は、膵管腺癌(PDAC)において高密度に増殖した間質の主要な構成要素であり、腫瘍の進行と薬剤耐性に寄与している。本研究は不均一な亜集団からなるCAFの新しい担癌マウスモデルを開発し、臨床的なヒトCAFの特性を再現した。また、CAFの分化に伴う細胞内代謝の再プログラミングを明らかにした。さらに、AD-MSCsが異なるCAFサブタイプに分化することを示し、CAFの役割を理解するための新しいマーカーも同定した。本研究はCAFの役割と機能に関する我々の理解を深め、将来的ながん治療法の開発に貢献する可能性がある。

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (13 results)

All 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (5 results) (of which Invited: 3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] A novel therapeutic strategy for pancreatic cancer: Targeting cell surface glycan using rBC2LC-N lectin-drug conjugate (LDC)2017

    • Author(s)
      Shimomura Osamu、Oda Tatsuya、Tateno Hiroaki、Ozawa Yusuke、Kimura Sota、Sakashita Shingo、Noguchi Masayuki、Hirabayashi Jun、Asashima Makoto、Ohkohchi Nobuhiro
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 17 Issue: 1 Pages: 183

    • DOI

      10.1158/1535-7163.mct-17-0232

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelet × CRP Multiplier Value as an Indicator of Poor Prognosis in Patients With Resectable Pancreatic Cancer2017

    • Author(s)
      Miyamoto Ryoichi、Oda Tatsuya、Hashimoto Shinji、Kurokawa Tomohiro、Kohno Keisuke、Akashi Yoshimasa、Ohara Yusuke、Yamada Keiichi、Enomoto Tsuyoshi、Ohkohchi Nobuhiro
    • Journal Title

      Pancreas

      Volume: 46 Issue: 1 Pages: 35-41

    • DOI

      10.1097/mpa.0000000000000697

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelet x CRP Multiplier Value as an Indicator of Poor Prognosis in Patients With Resectable Pancreatic Cancer.2017

    • Author(s)
      Miyamoto R, Oda T, Hashimoto S, Kurokawa T, Kohno K, Akashi Y, et al.
    • Journal Title

      Pancreas.

      Volume: 46(1) Pages: 35-41

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis.2016

    • Author(s)
      Ohara Y, Oda T, Hashimoto S, Akashi Y, Miyamoto R, Enomoto T, et al.
    • Journal Title

      World J Gastroenterol

      Volume: 22(38) Pages: 8596-8604

    • NAID

      120007129264

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cetuximab delivery and antitumor effects are enhanced by mild hyperthermia in a xenograft mouse model of pancreatic cancer.2016

    • Author(s)
      Miyamoto R, Oda T, Hashimoto S, Kurokawa T, Inagaki Y, Shimomura O, et al.
    • Journal Title

      Cancer Sci

      Volume: 107(4) Issue: 4 Pages: 514-520

    • DOI

      10.1111/cas.12888

    • NAID

      120007135356

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Well leg compartment syndrome after surgery for ulcerative colitis in the lithotomy position: A case report.2016

    • Author(s)
      Enomoto T, Ohara Y, Yamamoto M, Oda T, Ohkohchi N.
    • Journal Title

      International journal of surgery

      Volume: 23 Pages: 25-8

    • NAID

      120007135335

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Novel therapeutic strategy for pancreatic cancer with lectin drug conjugate (LDC) ~ the Efficacy and pilot Safety test~2018

    • Author(s)
      Osamu Shimomura, Tatsuya Oda, Hiroaki Tateno, Yusuke Ozawa, Sota Kimura, Shigo Sakashita, Jun Hirabayashi, Masayuki Noguchi, Makoto Asashima, Nobuhiro Ohkohchi
    • Organizer
      AACR(米国癌学会総会) 2018
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] レクチン薬剤複合体を用いた膵癌細胞表面糖鎖をターゲットにした新規癌治療2018

    • Author(s)
      下村 治、小田竜也、舘野浩章、小澤祐介、木村壮大、坂下信悟、野口雅之、平林 淳、浅島 誠、大河内信弘
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Application of a lectin as a drug carrier for glycan-targeting cancer therapy2017

    • Author(s)
      Tatsuya Oda, Osamu Shimomura, Hiroaki Tateno, Yusuke Ozawa, Jun Hirabayashi and Nobuhiro Ohkohchi.
    • Organizer
      AACR(米国癌学会総会) 2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Pancreatic cancer specific glycosylation survey by a panel of lectin staining; Tn antigen exposure as a result of o-glycan truncation.2017

    • Author(s)
      Yusuke Ozawa, Tatsuya Oda, Osamu Shimomura, Hiroaki Tateno, Jun Hirabayashi Nobuhiro Ohkohchi
    • Organizer
      AACR (米国癌学会総会) 2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 糖結合タンパク「レクチン」をキャリアーとした新規癌治療法の開発2017

    • Author(s)
      下村 治、小田竜也、舘野浩章、平林 淳、鄭 允文、大河内信弘
    • Organizer
      第72回日本消化器外科学会総会
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] がんの診断及び治療方法2017

    • Inventor(s)
      舘野浩章,平林淳,浅島誠, 小田竜也,大河内信弘,下村治
    • Industrial Property Rights Holder
      舘野浩章,平林淳,浅島誠, 小田竜也,大河内信弘,下村治
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] がんの診断及び治療方法2016

    • Inventor(s)
      小田竜也、舘野浩章、平林淳、他5名
    • Industrial Property Rights Holder
      小田竜也、舘野浩章、平林淳、他5名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-069683
    • Filing Date
      2016-03-30
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2025-01-30  

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