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Elucidation of the Mechanism of Oral Cancer Development Starting from NETs ~Crosstalk between Oral Bacteria and Nicotine~

Research Project

Project/Area Number 20K10289
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57080:Social dentistry-related
Research InstitutionTohoku University

Principal Investigator

NISHIOKA TAKASHI  東北大学, 歯学研究科, 講師 (50641875)

Co-Investigator(Kenkyū-buntansha) 多田 浩之  東北大学, 歯学研究科, 講師 (70431632)
伊原木 聰一郎  岡山大学, 医歯薬学域, 教授 (80549866)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsニコチン / NETs / 口腔がん / 口腔細菌 / 細菌感染
Outline of Research at the Start

好中球の新たな機能として、好中球細胞外トラップ Neutrophil extracellular traps (NETs)が注目されている。近年、NETsは、好中球に細菌感染のみならずニコチンの刺激が加わることで誘導されること、NETs産生を起点としてがん細胞の増殖や転移が促進されることなどが明らかとなった。本研究では1.細菌感染によってバリア破綻した口腔粘膜においてNETs産生はがん発生の起点とるのか、2.ニコチン刺激が加わることによって、がん発生や増殖は促進されるのかを分子機構学的に明らかにすることを目的とする。

Outline of Final Research Achievements

Neutrophil extracellular traps (NETs), which have attracted attention as a new function of neutrophils, have various functions. In this study, we investigated the mechanisms underlying the disruption of the oral mucosal barrier by bacterial infection and nicotine and the induction of inflammation by NETs, focusing on the fact that neutrophils are induced not only by bacterial infection but also by nicotine stimulation and that the production of NETs promotes cancer cell proliferation and metastasis. We investigated the behavior of NETs by nicotine stimulation of human promyelocytic cell line (HL-60 cells) differentiated into neutrophils by retinoic acid treatment.

Academic Significance and Societal Importance of the Research Achievements

タバコは明らかなリスクファクターとして広く認識され、単一で最大の生活習慣病の原因である。タバコの構成主成分の1つであるニコチンは、自身の発がん性は証明されていないものの喫煙者の血中に高濃度で存在し、口腔がんや歯周病において影響をおよぼす。本研究は、NETsとニコチンの関係に焦点をあて、口腔がん発生メカニズムの解明に寄与したい。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2023 2022 2021 Other

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

  • [Int'l Joint Research] Northeastern University(米国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Macrophage migration inhibitory factor-mediated mast cell extracellular traps induce inflammatory responses upon Fusobacterium nucleatum infection2023

    • Author(s)
      Tada, H., Nishioka, T., Ishiyama, R., Song, LT., Onoue, S., Kawahara, K., Nemoto, E., Matsushita, K., Sugawara, S.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 674 Pages: 90-96

    • DOI

      10.1016/j.bbrc.2023.06.060

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reactivation of p53 by RITA Induces Apoptosis in Human Oral Squamous Cell Carcinoma Cells2022

    • Author(s)
      ENDO MANABU、NISHIOKA TAKASHI、NUMAZAKI KENTO、HASEGAWA HIROSHI、TAKAHASHI TETSU、SUGAWARA SHUNJI、TADA HIROYUKI
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 6 Pages: 2931-2937

    • DOI

      10.21873/anticanres.15775

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Root canal narrowing patterns of mandibular first premolars on panoramic radiographs according to the number of root canals diagnosed on cone beam computed tomographic images2022

    • Author(s)
      Shimada Yusuke、Kojima Ikuho、Nishioka Takashi、Sakamoto Maya、Iikubo Masahiro
    • Journal Title

      Odontology

      Volume: 111 Issue: 1 Pages: 172-177

    • DOI

      10.1007/s10266-022-00713-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hericium erinaceus ethanol extract and ergosterol exert anti-inflammatory activities by neutralizing lipopolysaccharide-induced pro-inflammatory cytokine production in human monocytes2022

    • Author(s)
      Tada Hiroyuki、Kawahara Kazuyoshi、Osawa Hiraku、Song Li-Ting、Numazaki Kento、Kawai Junya、Onoue Sakura、Nishioka Takashi、Nemoto Eiji、Matsushita Kenji、Sugawara Shunji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 636 Pages: 1-9

    • DOI

      10.1016/j.bbrc.2022.10.090

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mapping of dental graduates’ career paths in Hong Kong, Japan and mainland China2022

    • Author(s)
      Jiang Chloe Meng、Nishioka Takashi、Hong Guang、Yu Hao、Zhang Chang-yuan、Chu Chun Hung
    • Journal Title

      Frontiers in Oral Health

      Volume: 3 Pages: 1-8

    • DOI

      10.3389/froh.2022.994613

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells.2021

    • Author(s)
      Song LT, Tada H, Nishioka T, Nemoto E, Imamura T, Potempa J, Li CY, Matsushita K, Sugawara S
    • Journal Title

      J Innate Immun

      Volume: Nov 25 Issue: 4 Pages: 1-14

    • DOI

      10.1159/000519737

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of the COVID‐19 pandemic on dental clinical training and future prospects2021

    • Author(s)
      Nishioka Takashi、Mayanagi Gen、Iwamatsu‐Kobayashi Yoko、Hong Guang
    • Journal Title

      Journal of Dental Education

      Volume: 85 Issue: S3 Pages: 1999-2001

    • DOI

      10.1002/jdd.12562

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 歯周病マウスモデルにおけるPorphyromonas gingivalisと好中球による脳機能障害の検討2023

    • Author(s)
      リュウ ドウシン、多田 浩之、西岡 貴志、松下 健二、菅原 俊二
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] The functional role of neutrophils in RANKL-induced osteoclastogenesis2023

    • Author(s)
      Numazaki, K., Tada, H., Nishioka, T., Matsushita, K., Mizoguchi, I., Sugawara, S
    • Organizer
      2023 Annual Meeting of ADEAP CA+inD International Symposium
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Neutrophil extracellular trapsのdouble-stranded DNAは破骨細胞分化を制御する2022

    • Author(s)
      沼崎 研人,西岡 貴志,松下 健二,多田 浩之
    • Organizer
      第27回日本エンドトキシン・自然免疫研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] Porphyromonas gingivalisジンジパインはヒト血管内皮細胞のPAI-1を分解し,血管内皮の創傷治癒を遅延させる2022

    • Author(s)
      多田 浩之,西岡 貴志,松下 健二,菅原 俊二
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Root canal narrowing patterns of mandibular first premolars on panoramic radiographs according to the number of root canals diagnosed on cone beam computed tomographic images2022

    • Author(s)
      Yusuke Shimada, Ikuho Kojima, Takashi Nishioka, Maya Sakamoto, Masahiro Iikubo
    • Organizer
      ACOMFR(アジア歯科顎顔面放射線学会)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2025-01-30  

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