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Polymer array scaffold-based creation of a new cell phenomics phase for cancer stem cell stratification

Research Project

Project/Area Number 20K21540
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Tabu Kouichi  東京医科歯科大学, 難治疾患研究所, 講師 (10466469)

Co-Investigator(Kenkyū-buntansha) 田賀 哲也  東京医科歯科大学, 難治疾患研究所, 教授 (40192629)
Project Period (FY) 2020-07-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsがん幹細胞 / 合成ポリマー / 人工微小環境 / 微小環境適合性 / オミクス / フェノミクス / polymerome / 層別化 / ポリマー嗜好性 / ポリメローム / 膠芽腫 / テモゾロミド / PCA / t-SNE / ポリマーmicroarray
Outline of Research at the Start

患者個人に最適な治療法の提供をめざす精密医療において、治療感受性や再発リスクを予測する層別化技術の開発は極めて重要な意義をもつ。その一方でそれら特性を担う細胞、すなわちがん幹細胞の個性を分類するための手法は未だ確立されていない。本研究は英国材料化学分野との共同研究を通じて確立された網羅的な人工微小環境探索系「ポリマーmicroarray」の手法を用いて、新規の表現型オミクス(フェノミクス)階層の創出に挑む。これにより従来の階層ではカバーされてこなかった「生きた細胞の微小環境適合性」という極めてユニークかつ重要な表現型に基づき、がん幹細胞のサブタイプ分類とそれに応じた層別治療法の開発を目指す。

Outline of Final Research Achievements

To develop the innovative diagnostic methods that predict therapy-resistance and recurrent risk (i.e. cancer stemness) in cancer patients, the binding preference of cells to hundreds of synthetic polymer microenvironments (named as “polymerome”) was compared. Cell lines with different gene alterations and different cells of origins displayed the apparently distinctive polymeromes. Further analysis demonstrated that this new cell-phenomics phase is useful to discriminate the chemoresistant feature of cancer patients to anti-cancer drugs.

Academic Significance and Societal Importance of the Research Achievements

治療抵抗性や再発リスクは層別化最大の目的でありながらも、それら特性を担う細胞(すなわちがん幹細胞)の層別法は未だ確立されていない。本研究で導出された新規のオミクス概念polymeromeは、網羅性を有する初めてのフェノミクス階層として従来のオミクス体系に変革をもたらすものであり、学術的に高い波及効果を有する。また、本研究で同定されたがん幹細胞診断ポリマーは、核酸・抗体に続く次世代の高分子シーズとして産業界に与えるインパクトも高く、将来的にがん研究・医療の方向性を大きく転換させる高い潜在性を有している。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (32 results)

All 2022 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] The University of Edinburgh(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] The University of Edinburgh(英国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] The University of Edinburgh(英国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Cancer ego-system in glioma: an iron-replenishing niche network systemically self-organized by cancer stem cells2022

    • Author(s)
      Tabu Kouichi、Taga Tetsuya
    • Journal Title

      Inflammation and Regeneration

      Volume: 42 Issue: 1 Pages: 54-54

    • DOI

      10.1186/s41232-022-00240-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapy-resistant nature of cancer stem cells in view of iron metabolism2022

    • Author(s)
      Wang Wenqian、Tabu Kouichi、Aimaitijiang Alapati、Taga Tetsuya
    • Journal Title

      Inflammation and Regeneration

      Volume: 42 Issue: 1 Pages: 34-34

    • DOI

      10.1186/s41232-022-00220-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer Stem Cell-Associated Immune Microenvironment in Recurrent Glioblastomas2022

    • Author(s)
      Murota Yoshitaka、Tabu Kouichi、Taga Tetsuya
    • Journal Title

      Cells

      Volume: 11 Issue: 13 Pages: 2054-2065

    • DOI

      10.3390/cells11132054

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glioma cells remotely promote erythropoiesis as a self‐expanding strategy of cancer stem cells2021

    • Author(s)
      Aimaitijiang Alapati、Tabu Kouichi、Wang Wenqian、Nobuhisa Ikuo、Taga Tetsuya
    • Journal Title

      Genes to Cells

      Volume: 27 Issue: 1 Pages: 25-42

    • DOI

      10.1111/gtc.12908

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Difference in the malignancy between RAS and GLI1-transformed astrocytes is associated with frequency of p27KIP1?positive cells in xenograft tissues2021

    • Author(s)
      Sasai Ken、Tabu Kouichi、Saito Takashi、Matsuba Yukio、Saido Takaomi C、Tanaka Shinya
    • Journal Title

      Pathology - Research and Practice

      Volume: 223 Pages: 153465-153465

    • DOI

      10.1016/j.prp.2021.153465

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [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 Research-status 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

      Pages: 122-127

    • Related Report
      2020 Research-status Report
  • [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 Research-status 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 Research-status 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 Research-status Report
  • [Presentation] Synthetic polymer microenvironment array chip based development of new cell phenomics for cancer stratification2022

    • Author(s)
      Kouichi Tabu, Shinji Kohsaka, Takuichiro Hide, Tetsuya Taga
    • Organizer
      The 81st Annual Meeting of the Japanese Cancer Association
    • Related Report
      2022 Annual Research Report
  • [Presentation] Establishment of a high-content screening system for niche mimicries using polymer-immobilized microwell array plates2022

    • Author(s)
      Yoshitaka Murota, Kouichi Tabu, Tetsuya Taga
    • Organizer
      The 81st Annual Meeting of the Japanese Cancer Association
    • Related Report
      2022 Annual Research Report
  • [Presentation] Exploration of glioma recurrence-related genes upregulated in highly invasive and 5-ALA-PDD escaping cells2022

    • Author(s)
      Tingting Zhang, Kouichi Tabu, Yoshitaka Murota, Takuichiro Hide, Shunichiro Ogura, Tetsuya Taga
    • Organizer
      The 81st Annual Meeting of the Japanese Cancer Association
    • Related Report
      2022 Annual Research Report
  • [Presentation] がん幹細胞ニッチ擬態性ハイドロゲルを用いた膵がん治療標的分子の探索2022

    • Author(s)
      椨 康一, 室田 吉貴, 永根 まり子, 田中 真二, 田賀 哲也
    • Organizer
      第43回日本炎症・再生医学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Identification of a niche-mimicking synthetic polymer scaffold that maintains neural stem cells in a growth factor- and serum-free system2022

    • Author(s)
      Tetsuya Taga, Norihisa Bizen, Kouichi Tabu, Mei Wu, Christian Mangani, Rong Zhang, Mark Bradley
    • Organizer
      The 19th Stem Cell Research Symposium
    • Related Report
      2022 Annual Research Report
  • [Presentation] Polymer based elucidation of molecular basis underlying cancer stem cell mediated niche reconstruction and glioma recurrence2021

    • Author(s)
      Kouichi Tabu, Tetsuya Taga
    • Organizer
      The 18 th Stem Cell Research Symposium
    • Related Report
      2021 Research-status Report
  • [Presentation] Niche-mimicking polymer-based characterization of human pancreatic cancer stem cells (pCSCs)2021

    • Author(s)
      Mariko Nagane, KouichiTabu, Yoshitaka Murota, Shinji Tanaka, Tetsuya Taga
    • Organizer
      The 18 th Stem Cell Research Symposium
    • Related Report
      2021 Research-status Report
  • [Presentation] 生物機能性高分子ハイドロゲルによるがん幹細胞ニッチ自己構築ならび にグリオーマ再発機構の解明2021

    • Author(s)
      椨 康一, 田賀 哲也
    • Organizer
      第42 回日本炎症・再生医学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒト膵癌幹細胞の特性解明のためのニッチ擬態ポリマーの開発と最適化2021

    • Author(s)
      永根まり子, 椨康一, 室田 吉貴, 田中真二, 田賀哲也
    • Organizer
      第42 回日本炎症・再生医学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Cancer stem cell niche-mimicking polymer-based exploration of the factors responsible for glioma recurrence2021

    • Author(s)
      Kouichi Tabu, Tetsuya Taga
    • Organizer
      The 80th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2021 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status Report
  • [Remarks] 東京医科歯科大学難治疾患研究所幹細胞制御分野ホームページ(日本語)

    • URL

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

    • Related Report
      2022 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ホームページ(English)

    • URL

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

    • Related Report
      2022 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ホームページ

    • URL

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

    • Related Report
      2021 Research-status Report 2020 Research-status Report

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Published: 2020-08-03   Modified: 2024-01-30  

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