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Elucidation of cancer stem cell niche components and signaling by bioactive polymer arrays

Research Project

Project/Area Number 18H02678
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TAGA Tetsuya  東京医科歯科大学, 難治疾患研究所, 教授 (40192629)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords生物機能性ポリマー / 癌幹細胞 / ニッチ / 脳腫瘍 / 神経膠芽腫 / 鉄代謝 / オートスキジス / 癌 / グリオーマ / 膵臓癌 / ポリマー
Outline of Final Research Achievements

This study has demonstrated the usefulness of synthetic polymer scaffolds as a tool for comprehensively elucidating glioma stem cell niche, by revealing iron that regulates glioma stem cell maintenance and glioma expansion. This finding provides a new self-expanding strategy of glioma stem cells that systemically exploits erythroid lineages to reconstruct GSC-friendly niche. In this study, it is also revealed that glioma stem cell-derived necrotic particles designated as autoschizis-like products play a key role in developing a glioma stem cell-supportive subset of tumor-associated macrophages. This finding thus demonstrates that glioma necrosis is not a meaningless death but is a tumor-beneficial event. Taken together, a series of these studies will provide new insights into the mechanisms underlying glioma stem cell-driven niche development as well as glioma progression and recurrence.

Academic Significance and Societal Importance of the Research Achievements

癌幹細胞は治療抵抗性を有し癌の進展や転移に寄与するため癌根絶において重要な治療標的として認識される。その微小環境である癌幹細胞ニッチの解明は癌幹細胞性の消失に向かわせる手掛かりになるが、癌幹細胞ニッチの構成要素は極めて多岐に渡るため全容解明は困難であった。本研究において、癌幹細胞を維持する働きをもつ生物機能性ポリマーを用いて鉄代謝という癌幹細胞ニッチ要素を同定したことを端緒にして癌幹細胞が生体の赤血球分化を利己的に制御してニッチを構築することおよび、癌幹細胞が特殊な細胞死を介して生体の免疫細胞に作用して利己的なニッチ構築を行うことを示した。これら2つの新規概念は学術的にも社会的にも意義深い。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (33 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (4 results)

  • [Int'l Joint Research] School of Chemistry, Univ. of Edinburgh(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] School of Chemistry, Univ. of Edinburgh(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] School of Chemistry, Univ. of Edinburgh(英国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer2021

    • Author(s)
      Suzuki I, Yoshida S, Tabu K, Kusunoki S, Matsumura Y, Izumi H, Asanoma K, Yagi H, Onoyama I, Sonoda K, Kohno K, Taga T, Itakura A, Takeda S, Kato K
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 4220-4220

    • DOI

      10.1038/s41598-021-83200-5

    • NAID

      120007044568

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 合成ポリマーを用いた癌幹細胞ニッチの特性解明2021

    • Author(s)
      椨康一、田賀哲也
    • Journal Title

      別冊・医学のあゆみ

      Volume: - Pages: 122-127

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Sox17-mediated expression of adherent molecules is required for the maintenance of undifferentiated hematopoietic cluster formation in midgestation mouse embryos2020

    • Author(s)
      Takahashi Satomi、Nobuhisa Ikuo、Saito Kiyoka、Gerel Melig、Itabashi Ayumi、Harada Kaho、Osawa Mitsujiro、Endo Takaho A.、Iwama Atsushi、Taga Tetsuya
    • Journal Title

      Differentiation

      Volume: 115 Pages: 53-61

    • DOI

      10.1016/j.diff.2020.08.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway2020

    • Author(s)
      Anani Maha、Nobuhisa Ikuo、Taga Tetsuya
    • Journal Title

      Journal of Cancer Prevention

      Volume: 25 Issue: 4 Pages: 204-212

    • DOI

      10.15430/jcp.2020.25.4.204

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glioma progression and recurrence involving maintenance and expansion strategies of glioma stem cells by organizing self-advantageous niche microenvironments2020

    • Author(s)
      Taga T and Tabu K
    • Journal Title

      Inflammation and Regeneration

      Volume: 40 Issue: 1 Pages: 33-33

    • DOI

      10.1186/s41232-020-00142-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 膠芽腫がん幹細胞ニッチの標的探索2020

    • Author(s)
      椨康一、田賀哲也
    • Journal Title

      Precision Medicine

      Volume: 3 Pages: 70-73

    • Related Report
      2020 Annual Research Report
  • [Journal Article] ニッチを標的とする膠芽腫がん幹細胞の制御2020

    • Author(s)
      椨康一、田賀哲也
    • Journal Title

      Medical Science Digest

      Volume: 46 Pages: 77-79

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Glioma stem cell (GSC)-derived autoschizis-like products confer GSC niche properties involving M1-like tumor-associated macrophages2020

    • Author(s)
      Tabu K, Liu W, Kosaku A, Terashima K, Murota Y, Aimaitijiang A, Nobuhisa I, Hide T and Taga T
    • Journal Title

      Stem Cells

      Volume: - Issue: 8 Pages: 921-935

    • DOI

      10.1002/stem.3193

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 合成ポリマーを用いたがん幹細胞ニッチの解析2020

    • Author(s)
      椨康一、田賀哲也
    • Journal Title

      医学のあゆみ

      Volume: 273 Pages: 474-479

    • Related Report
      2019 Annual Research Report
  • [Presentation] Synthetic polymer-based stratification of soft tissue sarcomas with different gene alterations and cells of origin2020

    • Author(s)
      Tabu K, Zhang S, Kosaku A, Venkateswaran S, Kohsaka S, Bradley M, Taga T
    • Organizer
      11th World Biomaterials Congress (WBC Virtual 2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fabrication of niche-mimicking polymer hydrogels to characterize human pancreatic cancer stem cells2020

    • Author(s)
      Nagane M, Tabu K, Murota Y, Tanaka S, Taga T
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A new stratification method for predicting chemosensitivities of soft tissue sarcomas using synthetic polymer microarray2020

    • Author(s)
      Kosaku A, Tabu K, Kohsaka S, Taga T
    • Organizer
      第79回日本癌学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Chemical fabrication of bio-functional polymer-hydrogels that mimic cancer stem cell niche2020

    • Author(s)
      Tabu K and Taga T
    • Organizer
      第79回日本癌学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 炎症性細胞の制御による癌幹細胞のニッチ構築2020

    • Author(s)
      田賀 哲也, 椨 康一
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Glioma stem cells promote erythroid differentiation in mouse bone marrow2020

    • Author(s)
      Aimaitijiang A, Tabu K, Wang W, Nobuhisa I, Taga T
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Role of the Rasip1 in the hematopoiesis of HSC-containing hematopoietic cluster cells in midgestation of mouse embryos2020

    • Author(s)
      Melig G, Nobuhisa I, Kiyoka S, Tsukahara R, Itabashi A, Kanai Y, Kanai M, Taga T
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Contribution of Rasip1 to the maintenance of hematopoietic activity of cluster-forming cells in midgestation mouse embryos2020

    • Author(s)
      Melig G, Nobuhisa I, Kiyoka S, Tsukahara R, Itabashi A, Kanai Y, Kanai M, Taga T
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Synthetic polymer-based stratification of soft tissue sarcomas with different gene alterations and cells of origin2020

    • Author(s)
      Tabu K, Zhang S, Kosaku A, Venkateswaran S, Kohsaka S, Bradley M, Taga T
    • Organizer
      11th World Biomaterials Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Autoschizis-like spontaneous necrosis mediates a self-expanding strategy of glioma stem cells by modulating tumor-associated macrophages.2019

    • Author(s)
      Tabu K, Liu, W, Hide T and Taga T
    • Organizer
      The 17th Stem Cell Research Sympodium
    • Related Report
      2019 Annual Research Report
  • [Presentation] Enhanced erythropoiesis in bone marrow of C6 glioma-bearing mice2019

    • Author(s)
      Aimaitijiang A, Tabu K, Wang W, Nobuhisa I and Taga T
    • Organizer
      The 17th Stem Cell Research Sympodium
    • Related Report
      2019 Annual Research Report
  • [Presentation] Visualization and validation of monocyte-recruiting cells as a potential target of glioma stem cells2019

    • Author(s)
      Tabu K and Taga T
    • Organizer
      The 78th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2019 Annual Research Report
  • [Presentation] Glioma stem cells modulate erythropoiesis in mouse bone marrow.2019

    • Author(s)
      Aimaitijiang A, Tabu K and Taga T
    • Organizer
      The 78th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2019 Annual Research Report
  • [Presentation] A self-expanding strategy of glioma stem cells via promoting the development of M1-like tumor-associated macrophages2019

    • Author(s)
      Tabu K, Liu W and Taga T
    • Organizer
      The 42nd Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of Treatment Strategies Targeting Cancer Stem Cells2019

    • Author(s)
      Taga T and Tabu K
    • Organizer
      The 3rd Meeting of International Society of Precision Cancer Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of a subpopulation of glioma cells with a potential for tumor niche development involving myeloid cells2018

    • Author(s)
      Tabu K and Taga T
    • Organizer
      The 16th Stem Cell Research Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] A monocyte-recruiting phenotype defines functional heterogeneity of glioma cells with stemness and chemoresistance2018

    • Author(s)
      Tabu K and Taga T
    • Organizer
      The 77th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京医科歯科大学 難治疾患研究所 幹細胞制御分野 研究内容

    • URL

      http://www.tmd.ac.jp/mri/scr/subjects/index.html

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] Dept Stem Cell Regulation, MRI, TMDU: Res Subject

    • URL

      http://www.tmd.ac.jp/mri/scr/english/subjects/index.html

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 研究情報データベース 基本情報 田賀哲也

    • URL

      http://reins.tmd.ac.jp/html/100007289_ja.html

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] Res. Information DB: Personnel Info.: TAGA Tetsuya

    • URL

      http://reins.tmd.ac.jp/html/100007289_en.html

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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