Therapeutic strategy against gastrointestinal cancers targeting nardilysin

• Project/Area Number: 24590914
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: KOMEKADO Hideyuki 京都大学, 医学(系)研究科(研究院), 非常勤講師 (90452359)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌 / 胃 / シェディング / 微小環境 / 胃癌 / 大腸癌 / 抗癌剤 / ナルディライジン

Outline of Final Research Achievements

In this study, we aimed to investigate the effect of nardilysin (NRDc) on gastric or colorectal cancer and to examine the possibility of novel therapeutic strategy targeting NRDc. Knockdown of NRDc suppressed cancer cell growth concomitantly with decreased secretion of inflammatory cytokines, enhanced interferon-response, and impaired cell cycle progression. Knockdown of NRDc also lead enhanced apoptosis and attenuated growth of gastric or colorectal cancer cells when treated with anti-cancer agents. Furthermore, anti-NRDc neutralizing antibody suppressed cancer cell growth. Thus, we demonstrated the role of NRDc during cancer development and obtained the clue to achieve novel therapeutic strategies against gastric or colorectal cancer.

Research Products

• [Journal Article] Deletion of nardilysin prevents the development of steatohepatitis and liver fibrosis. (2014)
  • Author(s): Ishizu-Higashi S, Seno H, Nishi E, Matsumoto Y, Ikuta K, Tsuda M, Kimura Y, Takada Y, Kimura Y, Nakanishi Y, Kanda K, Komekado H, Chiba T.
  • Journal Title: Plos One Volume: 9 Issue: 5 Pages: e98017-e98017
  • DOI: 10.1371/journal.pone.0098017
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dclk1 distinguishes between tumor and normal stem cells in the intestine. (2013)
  • Author(s): Yuki Nakanishi, et. al.
  • Journal Title: Nature Genetics Volume: 45 Issue: 1 Pages: 98-103
  • DOI: 10.1038/ng.2481
  • Peer Reviewed
• [Journal Article] Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signaling via enhanced ectodomain shedding of TNF-a (2012)
  • Author(s): Kanda K, Komekado H, Kawada M, et al
  • Journal Title: EMBO Molecular Medicine Volume: (印刷中) Issue: 5 Pages: 396-411
  • DOI: 10.1002/emmm.201200216
  • Peer Reviewed
• [Presentation] NardilysinはTNF-aのシェディングを促進し、腸炎を増悪させる
  • Author(s): 神田啓太郎
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都）