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Genome-wide screening of the key molecules for metastasizing collagen VII-deficient squamous cell carcinoma.

Research Project

Project/Area Number 19K08764
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionHokkaido University

Principal Investigator

Nakamura Hideki  北海道大学, 医学研究院, 助手 (60435956)

Co-Investigator(Kenkyū-buntansha) 西江 渉  北海道大学, 医学研究院, 客員教授 (20443955)
柳 輝希  北海道大学, 大学病院, 講師 (50755973)
泉 健太郎  北海道大学, 医学研究院, 助教 (50793668)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsVII型コラーゲン / 有棘細胞癌 / 遠隔転移 / 網羅的ゲノムスクリーニング / CRISPR/Cas9
Outline of Research at the Start

COL7発現をノックアウトした不死化角化細胞(HaCaT細胞)の19,500種類の遺伝子を、1細胞につき1遺伝子ずつランダムにゲノム編集し、癌化し浸潤・転移を来した細胞から標的となった遺伝子を次世代シークエンサーを用いて同定する。独創的な手法で、DEB関連SCCの浸潤・遠隔転移機構の解明を目指す

Outline of Final Research Achievements

The aim of this study was to elucidate the metastatic mechanism of squamous cell carcinoma (SCC) arising in patients with dystrophic epidermolysis bullosa (DEB) caused by mutations in type 7 collagen (COL7) gene. DEB patient model keratinocytes with a comprehensive gene-editing did not develop metastasis when transplanted subcutaneously in mice, but the subcutaneous tumors of DEB patient model showed an overall irregular structure, surrounding fibrosis, and hypervascularization compared to subcutaneous tumors of normal keratinocytes. These results suggest that subcutaneous tumors in DEB patient model induce changes in the surrounding tissue environment via abnormal construction of the basement membrane, and that these changes may contribute to the metastatic mechanism of SCC in DEB patients.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、栄養障害型表皮水疱症患者(DEB)の表皮細胞は癌化する前に血管増生などの遠隔転移に繋がる組織環境を作ることが明らかとなった。今までは、線維芽細胞が主に関連するTGF-βの持続的な活性化に伴う慢性炎症がDEB患者の表皮細胞を取り囲む組織環境を変化させていると考えられてきた。本研究で得られた、DEB患者の表皮細胞自体が周囲の組織環境を遠隔転移しやすいように変化させる新たな知見は、今後DEB患者の表皮細胞を標的とした有棘細胞癌の予防法や治療法の可能性を示唆する。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] Hair follicle stem cell progeny heal blisters while pausing skin development2021

    • Author(s)
      Fujimura Yu、Watanabe Mika、Ohno Kota、Kobayashi Yasuaki、Takashima Shota、Nakamura Hideki、Kosumi Hideyuki、Wang Yunan、Mai Yosuke、Lauria Andrea、Proserpio Valentina、Ujiie Hideyuki、Iwata Hiroaki、Nishie Wataru、Nagayama Masaharu、Oliviero Salvatore、Donati Giacomo、Shimizu Hiroshi、Natsuga Ken
    • Journal Title

      EMBO reports

      Volume: 22 Issue: 7

    • DOI

      10.15252/embr.202050882

    • NAID

      120007182923

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intravenous allogeneic multilineage‐differentiating stress‐enduring cells in adults with dystrophic epidermolysis bullosa: a phase 1/2 open‐label study2021

    • Author(s)
      Fujita Y.、Nohara T.、Takashima S.、Natsuga K.、Adachi M.、Yoshida K.、Shinkuma S.、Takeichi T.、Nakamura H.、Wada O.、Akiyama M.、Ishiko A.、Shimizu H.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 35 Issue: 8

    • DOI

      10.1111/jdv.17201

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Zonula occludens-1 demonstrates a unique appearance in buccal mucosa over several layers2021

    • Author(s)
      Imafuku Keisuke、Kamaguchi Mayumi、Natsuga Ken、Nakamura Hideki、Shimizu Hiroshi、Iwata Hiroaki
    • Journal Title

      Cell and Tissue Research

      Volume: 384 Issue: 3 Pages: 691-702

    • DOI

      10.1007/s00441-021-03425-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electron Microscopic and Immunohistochemical Findings of the Epidermal Basement Membrane in Two Families with Nail-patella Syndrome2019

    • Author(s)
      Shinkuma S、Nakamura H、Maehara M、Takashima S、Nomura T、Fujita Y、Hasegawa S、Sato-Matsumura K、Abe R、Shimizu H
    • Journal Title

      Acta Dermato Venereologica

      Volume: 99(12) Pages: 1110-1115

    • DOI

      10.2340/00015555-3318

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cultured Epidermal Autografts from Clinically Revertant Skin as a Potential Wound Treatment for Recessive Dystrophic Epidermolysis Bullosa2019

    • Author(s)
      Matsumura Wakana、Fujita Yasuyuki、Shinkuma Satoru、Suzuki Shotaro、Yokoshiki Saki、Goto Hideki、Hayashi Hiroshi、Ono Kota、Inoie Masukazu、Takashima Shota、Nakayama Chihiro、Nomura Toshifumi、Nakamura Hideki、Abe Riichiro、Sato Norihiro、Shimizu Hiroshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 139(10) Issue: 10 Pages: 2115-2124.e11

    • DOI

      10.1016/j.jid.2019.03.1155

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficient gene reframing therapy for recessive dystrophic epidermolysis bullosa using CRISPR/Cas92019

    • Author(s)
      Takashima Shota、Shinkuma Satoru、Fujita Yasuyuki、Nomura Toshifumi、Ujiie Hideyuki、Natsuga Ken、Iwata Hiroaki、Nakamura Hideki、Vorobyev Artem、Abe Riichiro、Shimizu Hiroshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: in press Issue: 8 Pages: 1711-1721

    • DOI

      10.1016/j.jid.2019.02.015

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Wnt/β-catenin signaling regulates hemidesmosomes in keratinocytes2021

    • Author(s)
      Kosumi H, Watanabe M, Shinkuma S, Nohara T, Fujimura Y, Tsukiyama T, Donati G, Nakamura H, Iwata H, Ujiie H, Natsuga K
    • Organizer
      The 46th Annual Meeting of The Japanese Society for Investigative Dermatology(Kyoto, Japan)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Wnt/β-cateninシグナルが表皮角化細胞のヘミデスモソームを制御する2021

    • Author(s)
      小住英之, 渡邉美佳, 新熊悟, 野原拓馬, 藤村悠, 築山忠維, Giacomo Donati, 岩田浩明, 中村秀樹, 氏家英之, 夏賀健.
    • Organizer
      第428回日本皮膚科学会北海道地方会(札幌、日本)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 毛包幹細胞の娘細胞は皮膚の発生を停止させながら表皮下水疱を治癒させる2021

    • Author(s)
      藤村悠, 渡邉美佳, 大野航太, 小林康明, 高島翔太, 中村秀樹, 小住英之, 王禹楠, 眞井洋輔, Andrea Lauria, Valentina Proserpio, 氏家英之, 岩田浩明, 西江渉, 長山雅晴, Salvatore Oliviero, Giacomo Donati, 清水宏, 夏賀健
    • Organizer
      第426回日本皮膚科学会北海道地方会(札幌、日本)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 成人栄養障害型表皮水疱症患者を対象としたMuse細胞製品CL2020の国内1/2相試験:52週までの安全性の検討2021

    • Author(s)
      藤田靖幸, 野原拓馬, 高島翔太, 夏賀健, 足立太起, 吉田憲司, 新熊悟, 武市拓也, 中村秀樹, 和田理, 秋山真志, 石河晃, 清水宏.
    • Organizer
      第72回日本皮膚科学会中部支部学術大会(奈良、日本)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Hair follicle stem cell progeny repair subepidermal blisters at the expense of skin development.2020

    • Author(s)
      Fujimura Y, Watanabe M, Ohno K, Kobayashi Y, Nakamura H, Lauria A, Proserpio V, Ujiie H, Iwata H, Nishie W, Nagayama M, Olivielo S, Donati G, Shimizu H, Natsuga K
    • Organizer
      The 45th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2020 Research-status Report
  • [Presentation] Efficient gene reframing therapy for recessive dystrophic epidermolysis bullosa with CRISPR/Cas92020

    • Author(s)
      Takashima S, Shinkuma S, Fujita Y, Nomura T, Ujiie H, Natsuga K, Iwata H, Nakamura H, Vorobyev A, Abe R, Shimizu H
    • Organizer
      The 45th Annual Meeting of the Japanese Society for Investigative Dermatology, Virtual Meeting
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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