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Does "humoral anticancer factor" secreted by normal epithelium cooperate with "cell competition" for cancer protection?

Research Project

Project/Area Number 17K18302
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Surgical dentistry
General anatomy (including histology/embryology)
Research InstitutionTokyo Medical and Dental University (2022)
Fukuoka Dental College (2017-2021)

Principal Investigator

Kitagawa Norio  東京医科歯科大学, 大学院医歯学総合研究科, 講師 (40628517)

Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords細胞競合 / EDAC / Macropinocytosis / ケラチン5 / ケラチン17 / 抗菌ペプチド / 癌 / ケラチノサイト / 中間径フィラメント / ケラチン17 / がん微小環境 / Nisin / 口腔潜在的悪性疾患 / keratinocyte / macropinocytosis / nisin / antimicrobial peptide / intermediate filament / coculture technique / necrosis / coculture / cell-competition / cancer / cell competition / liquid factor / exosome / 組織学 / 解剖学 / 細胞骨格 / エクソソーム
Outline of Final Research Achievements

Recent studies have shown that normal epithelial cells sense and actively eliminate neighboring cancer cells using physical forces without the help of immune cells. Although humoral anticancer factors seem to contribute to this elimination, there is a dearth of knowledge on the topic. Thus, we analyzed the effect of nisin, a humoral anticancer factor, on epithelial cells. Nisin treatment altered keratin (K)5 and K17 distribution in the cells, making them spherical, along with actin incorporation. Since the spherical distribution was >1 μm in diameter, the possibility of a macropinocytosis-like phenomenon was indicated. Nisin was effective under experimental conditions wherein micropinosome-like structures were not observed. Nisin administration induced derangement of the cell membrane, such as flip-flop, and disruption of the transmembrane structure of the keratins and desmosome protein.

Academic Significance and Societal Importance of the Research Achievements

Macropinocytosisはアクチンとの関係が着目されることが多く、ケラチン(K)5、K17がMacropinocytosis様構造を包む報告は今までになく新規性がある。Macropinocytosisは癌細胞の代謝において重要な役割を果たすことが知られている。また、微小環境での癌細胞の生存に関係することから、癌の悪性度とも関連すると考えられており、微小環境でのMacropinocytosis様反応についてさらに解析していく必要性が示唆された。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2022 2020 2019 2018 2017 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 2 results) Remarks (2 results)

  • [Journal Article] Antimicrobial peptide nisin induces spherical distribution of macropinocytosis-like cytokeratin 5 and cytokeratin 17 following immediate derangement of the cell membrane2022

    • Author(s)
      Kitagawa Norio
    • Journal Title

      Anatomy & Cell Biology

      Volume: 55 Issue: 2 Pages: 190-204

    • DOI

      10.5115/acb.21.168

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Keratin 17-positive Civatte bodies in oral lichen planus?distribution variety, diagnostic significance and histopathogenesis2020

    • Author(s)
      Abe Tatsuya、Kitagawa Norio、Yoshimoto Shohei、Maruyama Satoshi、Yamazaki Manabu、Inai Tetsuichiro、Hashimoto Shuichi、Saku Takashi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 14586-14586

    • DOI

      10.1038/s41598-020-71496-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The reduced susceptibility of mouse keratinocytes to retinoic acid may be involved in the keratinization of oral and esophageal mucosal epithelium.2019

    • Author(s)
      Miyazono S, Otani T, Ogata K, Kitagawa N, Iida H, Inai Y, Matsuura T, Inai T
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 153 Issue: 4 Pages: 225-237

    • DOI

      10.1007/s00418-020-01845-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nisin, a food preservative produced by Lactococcus lactis, affects the localization pattern of intermediate filament protein in HaCaT cells2018

    • Author(s)
      Kitagawa Norio、Otani Takahito、Inai Tetsuichiro
    • Journal Title

      Anatomical Science International

      Volume: 94 Issue: 2 Pages: 163-171

    • DOI

      10.1007/s12565-018-0462-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum affects keratinization and tight junctions in three-dimensional cultures of the mouse keratinocyte cell line COCA through retinoic acid receptor-mediated signaling2018

    • Author(s)
      Ozaki Akane、Otani Takahito、Kitagawa Norio、Ogata Kayoko、Iida Hiroshi、Kojima Hiroshi、Inai Tetsuichiro
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 151 Issue: 4 Pages: 315-326

    • DOI

      10.1007/s00418-018-1741-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞底面に着目した癌細胞排除機構の研究2020

    • Author(s)
      北河憲雄
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ケラチノサイトに対する抗菌ペプチドの作用2020

    • Author(s)
      北河 憲雄、大谷 崇仁、緒方 佳代子、稲井 哲一朗
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ケラチノサイト細胞塊形成に対する 抗菌ペプチド Nisin の作用2019

    • Author(s)
      北河憲雄, 大谷崇仁, 緒方佳代子, 稲井哲一朗
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effect of antimicrobial peptide Nisin on keratinocytes2018

    • Author(s)
      Kitagawa N, Otani T, Ogata K, Inai T
    • Organizer
      Asia Pacific International Congress of Anatomists
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Stress activated mitogen-activated protein kinases affect tight junctions in K38 mouse keratinocyte cells2018

    • Author(s)
      Nikaido M, Otani T, Kitagawa N, Iida H, Anan H, Inai T
    • Organizer
      20th KACD-JSCD Joint Scientific Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ケラチノサイト液性因子による癌細胞排除の研究2018

    • Author(s)
      北河憲雄, 大谷崇仁, 緒方佳代子, 稲井哲一朗
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 血清がケラチノサイトの角化,分化およびタイト結合に及ぼす影響についての解析2018

    • Author(s)
      尾崎茜, 北河憲雄, 大谷崇仁, 緒方佳代子, 瀬尾皓, 小島寛, 稲井哲一朗
    • Organizer
      第45回福岡歯科大学学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] ストレス応答MAPキナーゼの活性化によるケラチノサイトのタイト結合についての解析2018

    • Author(s)
      二階堂美咲, 北河憲雄, 大谷崇仁, 緒方佳代子, 瀬尾皓, 阿南壽, 稲井哲一朗
    • Organizer
      第45回福岡歯科大学学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effect of antimicrobial peptide Nisin on keratinocytes2018

    • Author(s)
      北河憲雄、大谷崇仁、稲井哲一朗
    • Organizer
      第123回 日本解剖学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Three dimensional culture system of mouse keratinocytes2017

    • Author(s)
      尾崎茜、北河憲雄、大谷崇仁、小島寛、稲井哲一朗
    • Organizer
      第73回 日本解剖学会 九州支部学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/Barriology/

    • Related Report
      2020 Research-status Report 2018 Research-status Report
  • [Remarks] 福岡歯科大学 生体構造学講座について

    • URL

      https://www.fdcnet.ac.jp/col/department_graduate_school/div_info/div_info_kouzou#sec01

    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2024-01-30  

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