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Elucidation of cancer growth mechanisms by C5a-C5aR axis

Research Project

Project/Area Number 17K11679
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNagoya City University

Principal Investigator

Imai Masaki  名古屋市立大学, 医薬学総合研究院(医学), 講師 (30440936)

Co-Investigator(Kenkyū-buntansha) 太田 里永子  愛知県がんセンター(研究所), その他部局等, 研究員 (30452460)
山崎 小百合  名古屋市立大学, 医薬学総合研究院(医学), 教授 (70567255)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsC5a / 補体 / 制御性T細胞 / 頭頸部癌 / 口腔癌
Outline of Final Research Achievements

C5a receptor (C5aR) is overexpressed in many cancer tissues, and binding of C5a to C5aR causes cancer growth, invasion and metastasis. We first examined whether C5aR expresses of the oral cancer cell lines or not, mRNA level of C5aR was highly detected. On the other hand, it has been reported that the C5a-C5aR system induces the differentiation of regulatory T cells (Treg cells) and invasion of Treg cells into cancer tissues. However, despite the reports that the C5a-C5aR system acts Treg cells, expression level of C5aR was very low on Treg cells.

Academic Significance and Societal Importance of the Research Achievements

多くの癌組織でC5a-C5aRシステムが癌の浸潤や転移に関わっているが、本研究では今まで明らかにされていない『口腔癌とC5a-C5aRシステムの関係』を明らかできることが特徴である。本研究で口腔癌の増殖にC5a-C5aRシステムの関与が示唆されたが、免疫系を制御するが制御性 T細胞の分化、浸潤に関与しなかったことから、腫瘍特異的なC5aR阻害剤を作成できれば副作用が少なく、高い抗腫瘍効果が得られると予想され、臨床応用への可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (24 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (21 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] Hyperglycemia is associated with psoriatic inflammation in both humans and mice2019

    • Author(s)
      Ikumi K, Odanaka M, Shime H, Imai M, Osaga S, Taguchi O, Nishida E, Hemmi H, Kaisho T, Morita A, Yamazaki S
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 印刷中 Issue: 6 Pages: 1329-1338

    • DOI

      10.1016/j.jid.2019.01.029

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulatory T cells expressing abundant CTLA-4 on the cell surface with a proliferative gene profile are key features of human head and neck cancer.2019

    • Author(s)
      Matoba T, Imai M, Ohkura N, Kawakita D, Ijichi K, Toyama T, Morita A, Murakami S, Sakaguchi S, Yamazaki S.
    • Journal Title

      International Journal of Cancer

      Volume: 144(11) Issue: 11 Pages: 2811-2822

    • DOI

      10.1002/ijc.32024

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ultraviolet B?Induced Maturation of CD11b-Type Langerin?Dendritic Cells Controls the Expansion of Foxp3+Regulatory T Cells in the Skin2017

    • Author(s)
      Yamazaki Sayuri、Odanaka Mizuyu、Nishioka Akiko、Kasuya Saori、Shime Hiroaki、Hemmi Hiroaki、Imai Masaki、Riethmacher Dieter、Kaisho Tsuneyasu、Ohkura Naganari、Sakaguchi Shimon、Morita Akimichi
    • Journal Title

      The Journal of Immunology

      Volume: 200 Issue: 1 Pages: 119-129

    • DOI

      10.4049/jimmunol.1701056

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Skin dendritic cells expressing a unique set of genes associated with immunological tolerance are specialized to expand thymus-derived Foxp3+ regulatory T cells upon ultraviolet B exposure2019

    • Author(s)
      Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
    • Organizer
      Japan-Singapore Skin International Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dermal dendritic cells present neo-self antigens induced by ultraviolet B exposure to expand Foxp3+ regulatory T cells2019

    • Author(s)
      Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
    • Organizer
      77th annual meeting of Society for investigative dermatology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulatory T cells with a distinctive feature expand through dermal dendritic cells in the ultraviolet B exposed skin2019

    • Author(s)
      Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
    • Organizer
      16th international workshop on Langerhans cells
    • Related Report
      2019 Annual Research Report
  • [Presentation] Functional characterization of regulatory T (Treg) cells in UVB-irradiated skin2019

    • Author(s)
      Hiroaki Shime, Mizuyu Odanaka, Masaki Imai, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita, Sayuri Yamazaki
    • Organizer
      第48回 日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Expression of complement anaphylatoxin receptor in the various subsets of dendritic cells2019

    • Author(s)
      Masaki Imai, Rieko Ohta, Sayuri Yamazaki
    • Organizer
      第48回 日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] C3a受容体アンタゴニストはヒストンにより惹起された急性肺障害を改善した2019

    • Author(s)
      石橋和晃、水野智博、長野文彦、今井優樹、丸山彰一、永松 正、水野 正司
    • Organizer
      第56回日本補体学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 頭頸部癌における制御性T細胞の新たな特徴。2019

    • Author(s)
      的場拓磨、今井優樹、大倉永也、川北大介、伊地知圭、遠山竜也、森田明理、村上信五、坂口志文、山崎小百合
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Extracellular histones decrease the expression of membrane complement regulators.2018

    • Author(s)
      Mizuno T, Nagano F, Mizuno M, Iwata A, Takahashi K, Tsuboi N, Maruyama S, Nagamatsu T, Imai M.
    • Organizer
      27th International Complement Workshop
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Foxp3+ regulatory T cells are expanded by ultraviolet B-exposed PD-L1+ skin dendritic cell expressing a unique set of genes in a CSF1-independent manner.2018

    • Author(s)
      Yamazaki S, Odanaka M, Nishioka A, Kasuya S, Shime H, Hemmi H, Imai M, Riethmacher D, Kaisho T, Ohkura N, Sakaguchi S, Morita A
    • Organizer
      International Investigative Dermatology 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dendritic cells expressing a unique set of genes associated with immunological tolerance are specialized to expand thymus-derived Foxp3+ regulatory T cells in the ultraviolet B-exposed skin.2018

    • Author(s)
      Yamazaki S, Odanaka S, Shime H, Imai M, Nishioka A, Hemmi H, Kaisho T, Ohkura N, Sakaguchi S, Morita M
    • Organizer
      第47回日本免疫学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Hyperglycemia is associated with psoriatic inflammation in both humans and mice.2018

    • Author(s)
      Odanaka M, Ikumi K, Shime H, Imai M, Taguchi O, Hemmi H, Kaisho T, Morita A, Yamazaki S
    • Organizer
      第47回日本免疫学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] A New Feature of Regulatory T Cells in Human Head and Neck Cancer.2018

    • Author(s)
      Matoba T, Imai M, Ohkura N, Kawakita D, Ijichi K, Toyama T, Morita A, Murakami S, Sakaguchi S, Yamazaki S
    • Organizer
      第47回日本免疫学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 致死性血栓症モデルにおける膜補体制御因子の発現解析。2018

    • Author(s)
      水野智博、長野文彦、水野正司、岩田歩実、高橋和男、坪井直毅、丸山彰一、今井優樹、永松 正
    • Organizer
      日本病院薬剤師会東海ブロック日本薬学会東海支部 合同学術大会2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 補体制御によるがん免疫療法の開発。2018

    • Author(s)
      今井優樹
    • Organizer
      第55回日本補体学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 細胞外ヒストンは細胞表面のCrryおよびCD59a発現を低下させる。2018

    • Author(s)
      水野智博、長野文彦、水野正司、岩田歩実、高橋和男、坪井直毅、 丸山彰一、永松 正、今井優樹
    • Organizer
      第55回日本補体学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ミエロイド系細胞における補体アナフィラトキシン受容体の発現解析。2018

    • Author(s)
      今井 優樹、辻村 幸平、太田 里永子、山崎 小百合
    • Organizer
      第28回日本樹状細胞研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 細胞外ヒストンは細胞表面の膜補体制御因子(CD59a)発現を低下させる。2018

    • Author(s)
      岩田歩実、水野智博、長野文彦、高橋和男、坪井直毅、丸山彰一、今井優樹、水野正司、永松 正
    • Organizer
      医療薬学フォーラム2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 細胞外ヒストンは血小板凝集を介して、補体を活性化させる2018

    • Author(s)
      近藤亜美、水野智博、長野文彦、岩田歩実、余吾菜摘、高橋和男、坪井直毅、丸山彰一、水野正司、永松 正、今井優樹
    • Organizer
      医療薬学フォーラム2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 補体活性化による腫瘍の分子標的治療薬の開発2017

    • Author(s)
      太田 里永子、葛島 清隆、藤田 禎三、岡田 秀親、今井 優樹
    • Organizer
      第53回日本補体学会
    • Related Report
      2017 Research-status Report
  • [Presentation] C5、C5aは細胞外ヒストンにより誘発された致死性血栓症を増悪する2017

    • Author(s)
      水野 智博、吉岡 憲吾、水野 正司、清水 美衣、長野 文彦、 奥田 知将、坪井 直毅、丸山 彰一、永松 正、今井 優樹
    • Organizer
      第53回日本補体学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 福井聡介、多和田光洋、鈴木康弘、松川宜久、今井優樹、丸山彰一、水野正司2017

    • Author(s)
      真菌性腹膜炎を発症した PD 患者腹膜組織における補体制御因子の発現分布
    • Organizer
      第53回日本補体学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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