卵巣癌においてＬＳＲが制御する脂質代謝経路の解析と抗ＬＳＲ抗体による阻害の検証

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19K16748
• Research Institution: Osaka University
• Principal Investigator: 平松 宏祐 大阪大学, 医学部附属病院, 助教 (10650591)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 卵巣癌 / LSR

Outline of Annual Research Achievements

①LSRの活性化条件とリガンドの同定
ヒト血清から超遠心法によりVLDLとLDLを抽出し、卵巣癌細胞株の増殖が促進することを証明した。
③腹膜播種におけるLSRと脂質の役割
ヒト血清から採取したVLDLとLDLはそれぞれ卵巣癌細胞株の遊走を促進した。また抗LSR抗体はこの作用を阻害した。
また昨年度と同様、子宮体癌細胞株を用いて実験を行った。昨年度はLSRのknockdownにより遊走能が低下することを証明していたが、遊走→接着→浸潤という腹膜播種の過程を評価するために浸潤能の評価を行った。結果、LSRのknockdownにより浸潤能は低下し、その経路はERK/MT1-MMP/MMP2を介して回路であることを証明した。さらにERKのknockdownでも同様の現象が起きることから、LSRを発端としMAPK経路を介した経路が子宮体癌の増殖、遊走に関連することを証明した。

Research Products

• [Presentation] 卵巣癌細胞膜発現タンパクであるLSRを標的とした新規抗体は卵巣癌の脂質代謝阻害やアポトーシス誘導により抗腫瘍効果を示す (2021)
  • Author(s): 平松宏祐
  • Organizer: 第63回日本婦人科腫瘍学会学術講演会
• [Presentation] Lipolysis-stimulated lipoprotein receptor regulates cell proliferation and invasion, and associates with poor prognosis in endometrial cancer. (2021)
  • Author(s): Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Mayu Shiomi, Tatsuo Masuda, Satoshi Nakagawa, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
  • Organizer: 第62回日本婦人科腫瘍学会学術講演会
• [Presentation] LSR is a novel prognostic factor by regulating cell proliferation via MEK/ERK pathway in endometrial cancer: Analysis of signal transduction, bioinformatics, and in vitro/in vivo study (2021)
  • Author(s): Yoshikazu Nagase, Kosuke Hiramatsu, Satoshi Nakagawa, Shinya Matsuzaki, Toshihiro Kimura, Satoshi Serada, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
  • Organizer: AACR ANNUAL MEETING 2021
  • Int'l Joint Research
• [Presentation] LSR is a novel therapeutic target via cell proliferation and invasion in endometrial cancer: analysis of signal transduction, bioinformatics, and in vitro/in vivo study (2021)
  • Author(s): Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Mayu Shiomi, Tatsuo Masuda, Satoshi Nakagawa, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
  • Organizer: 第73回日本産科婦人科学会学術講演会
• [Presentation] LSR activates MEK/ERK pathway and promotes cell proliferation and invasion in endometrial cancer: Analysis of bioinformatics-based signal transduction (2021)
  • Author(s): Yoshikazu Nagase, Kosuke Hiramatsu, Satoshi Nakagawa, Shinya Matsuzaki, Toshihiro Kimura, Satoshi Serada, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
  • Organizer: 第63回日本婦人科腫瘍学会学術講演会
• [Presentation] LSR activates MAPK pathway and promotes cell proliferation and invasion in endometrial cancer : Analysis of bioinformatics-based signal transduction (2021)
  • Author(s): Yoshikazu Nagase, Kosuke Hiramatsu, Satoshi Nakagawa, Shinya Matsuzaki, Toshihiro Kimura, Satoshi Serada, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
  • Organizer: IGCS (International Gynecologic Cancer Society) Annual Global Meeting 2021
  • Int'l Joint Research
• [Presentation] LSR activates MAPK signaling pathway and MMPs in endometrial cancer: in-vitro/in-vivo and bioinformatic analysis (2021)
  • Author(s): Yoshikazu Nagase, Kosuke Hiramatsu, Satoshi Nakagawa, Shinya Matsuzaki, Toshihiro Kimura, Satoshi Serada, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
  • Organizer: 第80回日本癌学会学術総会
• [Presentation] LSR promotes tumor progression by regulating signal transduction of apoptosis and ferroptosis in endometrial cancer (2021)
  • Author(s): Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Satoshi Nakagawa, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Satoshi Serada, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
  • Organizer: 22nd European Congress on Gynaecological Oncology of ESGO
  • Int'l Joint Research