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Dead cell-mediated activation mechanisms in oral cancer: Exploring the changes in lipid quality by dead cell phagocytosis

Research Project

Project/Area Number 21K09856
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionNiigata University

Principal Investigator

Yamazaki Manabu  新潟大学, 医歯学系, 准教授 (10547516)

Co-Investigator(Kenkyū-buntansha) 阿部 達也  新潟大学, 医歯学系, 助教 (70634856)
丸山 智  新潟大学, 医歯学総合病院, 講師 (30397161)
冨原 圭  新潟大学, 医歯学系, 教授 (70404738)
泉 健次  新潟大学, 医歯学系, 教授 (80242436)
田沼 順一  新潟大学, 医歯学系, 教授 (20305139)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords脂質 / 死細胞 / 口腔がん / 死細胞貪食 / 脂質クオリティ / コレステロール / 細胞死 / 貪食
Outline of Research at the Start

本研究の目的は、がん細胞が持つ高い死細胞貪食能が脂質の取り込みに関与している可能性を検証し、がん細胞機能に及ぼす影響を明らかにすることである。本研究では、死細胞貪食によってもたらされる細胞内脂質の量および質の変化を包括的に解析し、がん細胞の増殖・遊走・浸潤に関連する細胞内シグナリングとの接点を見出すことで、死細胞貪食を起点としたがん進展機構を標的化した制癌戦略への展望を探索したい。

Outline of Final Research Achievements

Cancer cells have a different lipid metabolism than normal cells, indicating the importance of understanding lipid quality (lipid composition) in cancer. We have previously investigated the possibility that the phenomenon of dead cell phagocytosis between oral cancer cells may contribute to tumor progression. In this study, we have shown that dead cell phagocytosis increases cholesterol amounts in cancer cells and that the increased cholesterol promotes polarity formation and cell migration ability of oral cancer cells, inducing plasma membrane localization of the cholesterol-binding protein caveolin-1 in the process.

Academic Significance and Societal Importance of the Research Achievements

死細胞によって誘導される口腔扁平上皮癌の活性化機序として、貪食した死細胞に由来するコレステロールの関与が明らかとなった。本研究の成果は、死細胞貪食機序ならびにコレステロール代謝をターゲットとした新規制癌治療法の創発につながる可能性がある。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (14 results)

All 2024 2023 2022 2021 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] 細胞内細胞構造“Cell-in-cell structures”の多様性と生物学的意義2024

    • Author(s)
      山﨑 学
    • Journal Title

      新潟歯学会雑誌

      Volume: 53 Pages: 1-4

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma2023

    • Author(s)
      Chan NN, Yamazaki M, Maruyama S, Abe T, Haga K, Kawaharada M, Izumi K, Kobayashi T, Tanuma JI.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 7 Pages: 6035-6035

    • DOI

      10.3390/ijms24076035

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis: a case report.2021

    • Author(s)
      Yamazaki M, Maruyama S, Abe T, Sumita Y, Katsumi Y, Nikkuni Y, Hayashi T, Tanuma JI.
    • Journal Title

      Journal of Medical Case Report

      Volume: 15 Issue: 1

    • DOI

      10.1186/s13256-021-03066-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crosstalk between oral squamous cell carcinoma cells and cancer-associated fibroblasts via the TGF-β/SOX9 axis in cancer progression2021

    • Author(s)
      Haga Kenta、Yamazaki Manabu、Maruyama Satoshi、Kawaharada Masami、Suzuki Ayako、Hoshikawa Emi、Chan Nyein Nyein、Funayama Akinori、Mikami Toshihiko、Kobayashi Tadaharu、Izumi Kenji、Tanuma Jun-ichi
    • Journal Title

      Translational Oncology

      Volume: 14 Issue: 12 Pages: 101236-101236

    • DOI

      10.1016/j.tranon.2021.101236

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Other iatrogenic immunodeficiency-associated lymphoproliferative disorders in the oral cavity: a clinicopathologic study of 4 cases and literature review2021

    • Author(s)
      Kawaharada Masami、Maruyama Satoshi、Ab? Tatsuya、Yamazaki Manabu、Kurokawa Akira、Katagiri Wataru、Takagi Ritsuo、Hayashi Takafumi、Kobayashi Tadaharu、Tanuma Jun-ichi
    • Journal Title

      Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

      Volume: 132 Issue: 6 Pages: 687-697

    • DOI

      10.1016/j.oooo.2021.05.015

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protumor role of estrogen receptor expression in oral squamous cell carcinoma cells2021

    • Author(s)
      Akyu Takei R, Tomihara K, Yamazaki M, Moniruzzaman R, Heshiki W, Sekido K, Tachinami H, Sakurai K, Yonesi A, Imaue S, Fujiwara K, Noguchi M.
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol.

      Volume: 132 Issue: 5 Pages: 549-565

    • DOI

      10.1016/j.oooo.2021.04.006

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Expression of heterotopic nucleic acid-sensing molecules in oral squamous cell carcinoma2024

    • Author(s)
      Yamazaki M, Abe T, Maruyama S, Tanuma JI.
    • Organizer
      第113回日本病理学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Dead tumor cells: Driving for progression of oral squamous cell carcinoma2023

    • Author(s)
      Yamazaki M.
    • Organizer
      The 21st International Congress of Oral Pathology and Medicine
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 口腔扁平上皮癌細胞におけるTLR4-NF-κB経路を介した死細胞誘導性活性化2022

    • Author(s)
      山崎 学, 阿部達也, 丸山 智, ニェイン ニェイン チャン, 河原田壮史, 田沼順一
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] コレステロールは口腔扁平上皮癌細胞の陽性を制御し遊走を促進する2022

    • Author(s)
      ニェイン ニェイン チャン, 山崎 学, 丸山 智, 阿部達也, 河原田壮史, 田沼順一
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Cholesterol promote migration of oral squamous cell carcinoma cells by regulating front-rear polarity2022

    • Author(s)
      ニェイン ニェイン チャン, 山崎 学, 丸山 智, 阿部達也, 河原田壮史, 田沼順一
    • Organizer
      第33回日本臨床口腔病理学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 死細胞によって誘導される口腔扁平上皮癌細胞の活性化機構2021

    • Author(s)
      山崎学, 阿部達也, 丸山智, Nyein Nyein Chan, 河原田壮史, 田沼順一
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 口腔扁平上皮癌における死細胞を起点とした腫瘍進展機序2021

    • Author(s)
      山崎学
    • Organizer
      第32回日本臨床口腔病理学会総会・学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Remarks] 口腔がん進展とコレステロールの関係が明らかに-コレステロールは口腔がん細胞の運動性を高める-

    • URL

      https://www.niigata-u.ac.jp/news/2023/376650/

    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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