Search for cell membrane marker protein specifically expressed in cancer-associated fibroblasts and its therapeutic application

• Project/Area Number: 18K19404
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kyushu University
• Principal Investigator: Michio Nakaya 九州大学, 薬学研究院, 准教授 (80464387)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 線維化 / 線維芽細胞 / 癌

Outline of Final Research Achievements

Cancer-associated fibroblasts, which are found around cancer cells, form the soil for cancer growth and invasion and worsen the disease. Recently, the development of cancer therapies targeting these cancer-associated fibroblasts has been attracting attention. On the other hand, no marker receptor that is strictly specific for cancer-associated fibroblasts has been found. We therefore searched for marker receptors specific for cancer-associated fibroblasts and identified candidate molecules.

Academic Significance and Societal Importance of the Research Achievements

すい臓がんなどの難知性がんにおいては、線維化は治療における大きな問題となっている。その線維化を実行する細胞ががん関連線維芽細胞である。従って、がん関連線維芽細胞はこれら難知性がんの治療の標的となる。私たちは、これまで同定されていなかった、がん関連線維芽細胞特異的なマーカー受容体候補を見出した。従って学術的な意味を持つと考える。また、この受容体を標的としてがん関連線維芽細胞特異的な薬剤送達が可能になるなど新たな難知性がん治療法開発への展開が見込まれ、社会的意義を持つと考える。

Research Products

• [Journal Article] Leukotriene B4 receptor 1 exacerbates inflammation following myocardial infarction. (2020)
  • Author(s): 1. Yuma Horii#, Michio Nakaya*#, Hiroki Ohara#, Hiroaki Nishihara#, Kenji Watari, Akiomi Nagasaka, Takeo Nakaya, Yuki Sugiura, Toshiaki Okuno, Tomoaki Koga, Akira Tanaka, Takehiko Yokomizo and Hitoshi Kurose
  • Journal Title: FASEB J Volume: in press
  • Peer Reviewed
• [Journal Article] Efferocytosis during myocardial infarction. (2020)
  • Author(s): Chikashi Yoshimura, Akiomi Nagasaka, Hitoshi Kurose, & Michio Nakaya
  • Journal Title: J.Biochem. Volume: in press
  • NAID: 40022279056
  • Peer Reviewed
• [Journal Article] Pancreatic carcinoma metastasis to a lung carcinoma lesion and pulmonary fibrotic regions, overtaking the stromal microenvironment (2019)
  • Author(s): 2. Takeo Nakaya, Masaya Sogabe, Shin-ichi Yamamoto, Kentaro Tsuji, Michio Nakaya, Toshiro Niki, Shunsuke Endo, and Akira Tanaka
  • Journal Title: Medicine Volume: e15888 Issue: 24 Pages: e15888-e15888
  • DOI: 10.1097/md.0000000000015888
  • Peer Reviewed
• [Journal Article] The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis. (2018)
  • Author(s): Iezaki T, Fukasawa K, Horie T, Park G, Robinson S, Nakaya M, Fujita H, Onishi Y, Ozaki K, Kanayama T, Hiraiwa M, Kitaguchi Y, Kaneda K, Yoneda Y, Takarada T, Guo XE, Kurose H, Hinoi E.
  • Journal Title: Development Volume: 145 Issue: 14 Pages: 164004-164004
  • DOI: 10.1242/dev.164004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complex formation between the vasopressin 1b receptor, β-arrestin-2, and the μ-opioid receptor underlies morphine tolerance (2018)
  • Author(s): Koshimizu TA, et al.
  • Journal Title: Nat Neurosci Volume: Epub ahead of print Issue: 6 Pages: 820-833
  • DOI: 10.1038/s41593-018-0144-y
  • Peer Reviewed
• [Presentation] 筋線維芽細胞に焦点を当てた線維化治療戦略 (2020)
  • Author(s): 仲矢道雄, 黒瀬等
  • Organizer: 日本薬学会第140年会
  • Invited
• [Presentation] 機械的刺激を感知し、組織の線維化を促進する転写共役因子の機能解析とそれを基盤とした新規線維化治療法の開発 (2019)
  • Author(s): 仲矢道雄
  • Organizer: 第1回日本メカノバイオロジー 研究会
• [Presentation] 心疾患時の死細胞貪食における筋線維芽細胞の役割 (2019)
  • Author(s): 仲矢道雄,
  • Organizer: 第61回日本結合組織学会
• [Presentation] プロトン感知性GPCR（GPR4）に着目した心筋梗塞時におけるpH低下の生理的影響の解析 (2019)
  • Author(s): 荻野瑠星、伊藤峻太、渡健治、長坂明臣、仲矢道雄、黒瀬等
  • Organizer: 生体機能と創薬シンポジウム2019
• [Presentation] Smad6を安定化させ、BMPシグナルを抑制するユビキチンリガーゼの同定 (2019)
  • Author(s): 廣中貴則、大場悠生、長坂明臣、仲矢道雄、黒瀬等
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2019
• [Presentation] Smad6を安定化し、BMPシグナルを抑制するユビキチンリガーゼの同定 (2019)
  • Author(s): 廣中貴則、大場悠生、長坂明臣、仲矢道雄、黒瀬等
  • Organizer: 第92回日本生化学会大会
• [Presentation] 筋線維芽細胞の機能を制御する新たな分子の探索と同定 (2019)
  • Author(s): 仲矢道雄
  • Organizer: 第3回 Fibrosis
  • Invited
• [Presentation] Phagocytosis of dead cells by myofibroblasts during myocardial infarction (2018)
  • Author(s): Michio Nakaya
  • Organizer: The 4th Japan-Taiwan Joint Symposium for Pharmaceutical Sciences
  • Int'l Joint Research / Invited
• [Presentation] 心疾患と死細胞貪食 (2018)
  • Author(s): 仲矢道雄
  • Organizer: 第16回レドックス・ライフイノベーションシンポジウム
  • Invited
• [Presentation] 心筋梗塞時の筋線維芽細胞による死細胞貪食 (2018)
  • Author(s): 仲矢道雄、黒瀬等
  • Organizer: 第50回 日本結合組織学会学術大会
  • Invited
• [Presentation] Identification of an E3 ubiquitin ligase that stabilizes Smad6 and inhibits BMP signaling (2018)
  • Author(s): Michio Nakaya, Yuki Ohba，Takanori Hironaka，Hidetaka Kosako，Hitoshi Kurose
  • Organizer: 12th International BMP Conference
  • Int'l Joint Research
• [Presentation] Cardiac myofibroblasts contribute to removal of dead cells from hypertrophic heart (2018)
  • Author(s): Michio Nakaya
  • Organizer: Japan Australia Meeting on Cell Death
  • Int'l Joint Research
• [Book] 生化学 「心筋梗塞時における死細胞貪食」 (2018)
  • Author(s): 仲矢道雄
  • Total Pages: 4
  • Publisher: 日本生化学会
• [Book] 医学のあゆみ 「心筋梗塞時の筋線維芽細胞による死細胞の貪食」 (2018)
  • Author(s): 仲矢道雄
  • Total Pages: 2
  • Publisher: 医歯薬出版株式会社
• [Remarks] 九州大学大学院薬学研究院 薬効安全性学分野
  • URL: http://chudoku.phar.kyushu-u.ac.jp
• [Remarks] 九州大学大学院 薬学研究院 薬効安全性学分野
  • URL: http://chudoku.phar.kyushu-u.ac.jp