New method for diagnosis for colon cancers by using stem cell as a target

• Project/Area Number: 26670377
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Shibasaki Yoshikazu 東京大学, 先端科学技術研究センター, 特任教授 (80196419)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: インビボイメージング / 幹細胞 / 大腸がん / EGFファミリー / EGF受容体 / 体外イメージング / ＥＧＦ

Outline of Final Research Achievements

Epiregulin (EPR) is a member of EGF family ligands and exert numerous cellular functions including stem cell stimulation. EPR is synthesized as a membrane-anchored protein (pro-EPR) and then proteolytically cleaved to yield a soluble form of EPR. While it is expressed at relatively low levels in most adult tissues, EPR is overexpressed in human colon, breast, and other cancers. We developed several anti-EPR monoclonal antibodies that specifically recognize human EPR, but not other EGF family ligands. Anti-EPR antibody is internalized into epiregulin expressing cancer cells. Using this system, we developed a mouse in vivo imaging system for epiregulin producing tumor. Our results suggest that anti-EPR antibodies represent valuable tools for medical imaging and for delivering agents for the treatment of cancers

Research Products

• [Journal Article] Epiregulin-blocking antibody inhibits epiregulin-dependent EGFR signaling (2017)
  • Author(s): Mariko Iijima, Motonobu Anai, Tatsuhiko Kodama, & Yoshikazu Shibasaki
  • Journal Title: BBRC Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Epiregulin Recognition Mechanisms by Anti-epiregulin Antibody 9E5: STRUCTURAL, FUNCTIONAL, AND MOLECULAR DYNAMICS SIMULATION ANALYSES. (2016)
  • Author(s): Kado Y1, Mizohata E2, Nagatoishi S3, Iijima M4, Shinoda K4, Miyafusa T3, Nakayama T2, Yoshizumi T2, Sugiyama A4, Kawamura T4, Lee YH4, Matsumura H2, Doi H4, Fujitani H4, Kodama T4, Shibasaki Y4, Tsumoto K5, Inoue T6.
  • Journal Title: J Biol Chem. Volume: 291 Issue: 5 Pages: 2319-2330
  • DOI: 10.1074/jbc.m115.656009
  • Peer Reviewed / Open Access / Int'l Joint Research