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The effects of nerves on the tumor microenvironment and tumor progression

Research Project

Project/Area Number 19K19160
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionOkayama University

Principal Investigator

Yoshida Saori  岡山大学, 大学病院, 助教 (80796467)

Project Period (FY) 2019-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords口腔がん / 腫瘍微小環境 / 神経 / 口腔扁平上皮癌 / 神経と腫瘍 / 骨髄移植マウス / 骨髄由来細胞
Outline of Research at the Start

(平成31年度)野生型マウスにGFPトランスジェニックマウスの骨髄細胞を移植したGFP骨髄移植マウスに対して、口腔癌を移植・定着させた腫瘍モデルマウスを作製する。この腫瘍モデルマウスを用いて、腫瘍組織の神経支配が腫瘍進展におよぼす効果、骨髄由来細胞の局所への誘導と分化、腫瘍微小環境構築への影響を、病理組織学的に検討する。
(平成32年度,33年度)同定された骨髄細胞動員因子を腫瘍モデルマウスに投与し、腫瘍進展効果について病理組織学的、細胞生物学的、分子生物学的に検討する。また同因子のアンタゴニストを用いた腫瘍増殖抑制を狙う。

Outline of Final Research Achievements

By transplanting bone marrow cells taken from GFP mice into wild-type mice, we created mice capable of tracking bone marrow cells. Furthermore, we subcutaneously transplanted human oral squamous cell carcinoma cell lines into the cheeks of nude mice to create tumor-bearing mice, and confirmed that tumors could be removed, tissue specimens could be prepared, and the tumor microenvironment could be examined using image analysis software. In the local nerve paralysis model mice, we initially planned to cut only one side of the nerve, but in order to minimize invasiveness, we succeeded in temporarily paralyzing the nerve locally by administering botulinum toxin. However, further adjustments are required to ensure that only the nerves are paralyzed and to determine the duration of paralysis, and these remain issues for the future.

Academic Significance and Societal Importance of the Research Achievements

神経分布は腫瘍の拡大様式に大きく関わり、腫瘍の進行度や予後を病理学的に診断する際の評価項目に含まれているが、腫瘍実質の増殖に対する神経の直接的な作用は不明な点が多い。神経と腫瘍進展の関係性が詳細に分かれば、神経や関連物質の遮断により腫瘍抑制が可能になる。口腔癌治療は外科的切除が第一選択だが、口腔は審美・発語・食事と患者のQOLに深く関わる部位であり、術後の患者の物理的・心理的負担は大きい。神経あるいは関連物質の遮断によって腫瘍の縮小が可能ならば、切除範囲を狭められるため審美や機能温存に大きく貢献できる。

Report

(7 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2024 2022 2021 2020 2019

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (11 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Efficacy of Cisplatin-CXCR4 Antagonist Combination Therapy in Oral Cancer2024

    • Author(s)
      Saori Yoshida, Hotaka Kawai, Yamin Soe, Htoo Shwe Eain, Sho Sanou, Kiyofumi Takabatake, Yohei Takeshita, Miki Hisatomi, Hitoshi Nagatsuka, Junichi Asaumi, Yoshinobu Yanagi
    • Journal Title

      Cancers

      Volume: 16 Pages: 2326

    • DOI

      10.3390/cancers16132326

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment2022

    • Author(s)
      May Wathone Oo, Hotaka Kawai, Kiyofumi Takabatake, Shuta Tomida, Takanori Eguchi, Kisho Ono, Qiusheng Shan, Toshiaki Ohara, Saori Yoshida, Haruka Omori, Shintaro Sukegawa, Keisuke Nakano, Kuniaki Okamoto, Akira Sasaki, and Hitoshi Nagatsuka
    • Journal Title

      JCI-insight

      Volume: 7(1) Pages: -

    • DOI

      10.1172/jci.insight.148960.

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer2019

    • Author(s)
      Yoshida Saori、Kawai Hotaka、Eguchi Takanori、Sukegawa Shintaro、Oo May Wathone、Anqi Chang、Takabatake Kiyofumi、Nakano Keisuke、Okamoto Kuniaki、Nagatsuka Hitoshi
    • Journal Title

      Cells

      Volume: 8 Pages: 761~761

    • DOI

      10.3390/cells8070761

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Notch Signaling Affects Oral Neoplasm Cell Differentiation and Acquisition of Tumor-Specific Characteristics2019

    • Author(s)
      Nakano Keisuke、Takabatake Kiyofumi、Kawai Hotaka、Yoshida Saori、Maeda Hatsuhiko、Kawakami Toshiyuki、Nagatsuka Hitoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Pages: 1973~1973

    • DOI

      10.3390/ijms20081973

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma2019

    • Author(s)
      Takabatake Kiyofumi、Shimo Tsuyoshi、Murakami Jun、Anqi Chang、Kawai Hotaka、Yoshida Saori、Wathone Oo May、Haruka Omori、Sukegawa Shintaro、Tsujigiwa Hidetsugu、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Pages: 5779~5779

    • DOI

      10.3390/ijms20225779

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation and roles of bone marrow?derived cells on the tumor microenvironment of oral squamous cell carcinoma2019

    • Author(s)
      Anqi Chang、Takabatake Kiyofumi、Kawai Hotaka、Oo May、Yoshida Saori、Fujii Masae、Omori Haruka、Sukegawa Shintaro、Nakano Keisuke、Tsujigiwa Hidetsugu、Jinhua Zheng、Nagatsuka Hitoshi
    • Journal Title

      Oncology Letters

      Volume: 18 Pages: 6628~6638

    • DOI

      10.3892/ol.2019.11045

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 口腔扁平上皮癌におけるシスプラチン-CXCR4阻害剤併用療法の有効性2021

    • Author(s)
      吉田 沙織, 河合 穂高, 長塚 仁, 竹下 洋平, 岡田 俊輔, 藤倉 満美子, 久富 美紀, 河津 俊幸, 浅海 淳一, 柳 文修
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] CT値を用いた歯原性嚢胞の鑑別の有用性と適応例の検討2020

    • Author(s)
      久富美紀,上原京憲,河津俊幸,岡田俊輔,竹下洋平,藤倉満美子,吉田沙織,藤田麻里子,柳文修,浅海淳一
    • Organizer
      第41回岡山歯学会総会・学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 口腔腫瘤性病変に対する超音波検査の有用性2020

    • Author(s)
      竹下洋平,河津俊幸,久富美紀,岡田俊輔,藤倉満美子,吉田沙織,難波友里,清水雄大,柳文修,浅海淳一
    • Organizer
      日本歯科放射線学会 第1回秋季学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 歯原性腫瘍・嚢胞のMRI診断2020

    • Author(s)
      河津俊幸,久富美紀,岡田俊輔,竹下洋平,藤倉満美子,吉田沙織,浅海淳一
    • Organizer
      日本歯科放射線学会第40回関西・九州合同地方会
    • Related Report
      2020 Research-status Report
  • [Presentation] Patient-derived xenograftモデルを用いた腫瘍間質による腫瘍実質の生物学的性格制御の検討2020

    • Author(s)
      高畠 清文, 河合 穂高, 大森 悠加, Oo May Wathone, 吉田 沙織, 中野 敬介, 長塚 仁
    • Organizer
      第74回日本口腔科学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 口腔扁平上皮癌の腫瘍微小環境における骨髄由来細胞の分化と役割2020

    • Author(s)
      高畠 清文, 河合 穂高, Oo May Wathone, 吉田 沙織, 大森 悠加, 中野 敬介, 辻極 秀次, 長塚 仁
    • Organizer
      第74回日本口腔科学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 口腔癌を取り巻く腫瘍微小環境に関する組織学的検討2020

    • Author(s)
      吉田沙織
    • Organizer
      日本病理学会100周年記念病理学研究新人賞二次審査
    • Related Report
      2020 Research-status Report
  • [Presentation] 口腔扁平上皮癌におけるCXCR4の腫瘍血管での役割2020

    • Author(s)
      大森悠加,河合穂高,吉田沙織,藤井昌枝,Qiusheng Shan,高畠清文,中野敬介,長塚 仁
    • Organizer
      第31回日本臨床口腔病理学会総会・学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 口腔扁平上皮癌におけるCXCR4の腫瘍血管新生への関与2019

    • Author(s)
      吉田沙織, 河合穂高, May Wathone Oo, Chang Anqi, 浜田芽衣, 高畠清文, 中野敬介, 長塚仁
    • Organizer
      日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] CXCR4の阻害が口腔扁平上皮癌の腫瘍血管に与える影響2019

    • Author(s)
      吉田沙織, 河合穂高, May Wathone Oo, Chang Anqi, 浜田芽衣, 高畠清文, 中野敬介, 長塚 仁
    • Organizer
      日本臨床口腔病理学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Relationship between PD-L1 Expression and clinicopathological classification in Tongue Cancer2019

    • Author(s)
      Saori Yoshida, May Wathone Oo, Hotaka Kawai, Kiyofumi Takabatake, Keisuke Nakano, Masanori Yasuda, Hitoshi Nagatsuka
    • Organizer
      The 4th International Symposium of Medical and Dental Education in Okayama
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2026-01-16  

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