Functional analysis of LSR and development of innovative therapy for ovarian cancer stem cells.

• Project/Area Number: 16K14637
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Kochi University
• Principal Investigator: NAKA TETSUJI 高知大学, 教育研究部医療学系臨床医学部門, 教授 (30303936)
• Co-Investigator(Renkei-kenkyūsha): FUJIMOTO MINORU 高知大学, 教育研究部・医療学系臨床医学部門, 准教授 (00379190) ; SERADA SATOSHI 高知大学, 医学部附属病院, 特任准教授 (50463302) ; YOSHINO KIYOSHI 大阪大学, 医学系研究科, 准教授 (90362730)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 卵巣癌 / 癌幹細胞 / LSR / 抗体療法

Outline of Final Research Achievements

Principal investigator’s (PI) group identified Lipolysis-stimulated lipoprotein receptor (LSR) as a new therapeutic target of ovarian cancer. LSR is one of the receptor of lipoprotein and located at cell surface, however, the function of LSR in cancer is still unclear. In this research, PI’s group demonstrated that in low glucose environment, LSR promoted lipoprotein uptake and contributed to cell proliferation/viability in vitro. Moreover, PI’s group also demonstrated that their newly developed anti-LSR monoclonal antibody inhibited these processes and showed anti-tumor effect in vitro and in vivo. In addition, the expression of CD44 which is one of the cancer stem cell related marker was decreased after administration of anti-LSR monoclonal antibody in vivo, suggesting that anti-LSR monoclonal antibody showed anti-tumor effect against cancer stem cell.

Research Products

• [Journal Article] LSR Antibody Therapy Inhibits Ovarian Epithelial Tumor Growth by Inhibiting Lipid Uptake (2018)
  • Author(s): Hiramatsu K, Serada S, Enomoto T, Takahashi Y, Nakagawa S, Nojima S, Morimoto A, Matsuzaki S, Yokoyama T, Takahashi T, Fujimoto M, Takemori H, Ueda Y, Yoshino K, Morii E, Kimura T, Naka T
  • Journal Title: Cancer Res Volume: 78 Issue: 2 Pages: 516-27
  • DOI: 10.1158/0008-5472.can-17-0910
  • Peer Reviewed / Open Access
• [Presentation] LSR promotes ovarian cancer cell growth following the activation of β-oxidation and its antibody inhibits lipid catabolism. ポスター発表(英語) (2017)
  • Author(s): Hiramatsu K, Serada S, Enomoto T, Yokoyama T, Takahashi Y, Fujimoto M, Yoshino K, Kimura T, Naka T.
  • Organizer: AACR Annual Meeting 2017 in Washington, D.C
  • Int'l Joint Research
• [Presentation] LSR promotes beta-oxidation via lipid uptake and subsequent tumor growth in ovarian cancer.口頭発表(英語) (2017)
  • Author(s): Hiramatsu K, Serada S, Fujimoto M, Matsuzaki S, Ueda Y, Yoshino K, Kimura T, Naka T.
  • Organizer: 第76回日本癌学会学術総会 パシフィコ横浜