Suppression of invasion of cancers by blocking ephrin-B1 mediated signaling

• Project/Area Number: 19590326
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Akita University (2008); National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East (2007)
• Principal Investigator: TANAKA Masamitsu Akita University, 医学部, 教授 (20291396)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: ephrin / Eph / スキルス癌 / シグナル伝達 / 治療

Research Abstract

Ephrin-B1のC末を介したシグナル伝達により、Arf1の活性化依存性にメタロプロテアーゼ(MMP-8)の細胞外分泌が促進されるメカニズムが同定できた。それを踏まえ、ephrin-B1のC末部分の合成ペプチドによって上記経路が遮断されること、およびヌードマウス腹腔内に同ペプチドを投与することでスキルス胃癌細胞の腹膜播種の抑制効果が確認された。Ephrin-B1の細胞内シグナル伝達の遮断が、スキルス胃癌などの組織浸潤、播種の阻止に有効である結果が得られた。

Research Products

• [Journal Article] A novel RNA-binding protein Ossa/C9orf10 regulates activity of Src kinases to protect cells from oxidative-stress induced apoptosis (2009)
  • Author(s): Tanaka M., Sasaki K., Kamata, R., Yanagihara K. and Sakai R.
  • Journal Title: Mol Cell Biol 29 Pages: 402-413
  • Peer Reviewed
• [Journal Article] A novel RNA binding protein Ossa/C9orf10 regulates activity of Src kinases to protect cells from oxidative-stress induced apoptosis (2009)
  • Author(s): Tanaka M., Sasaki K., Kamata, R.,Yanagihara K., and Sakai R.
  • Journal Title: Mol Cell Biol 29 Pages: 402-413
  • Peer Reviewed
• [Journal Article] CDCP1 regulates peritoneal dissemination of gastric scirrhous carcinoma (2008)
  • Author(s): Uekita T., Tanaka M., Takigahira M., Miyazawa Y., Kanai Y., Yanagihara K. Sakai R.
  • Journal Title: American Journal of Pathology 172 Pages: 1729-1739
  • Peer Reviewed
• [Journal Article] CDCP1 regulates peritoneal dissemination of gastric scirrhous carcinoma (2008)
  • Author(s): Uekita T., Tanaka M., Takigahira M., Miyazawa Y., Kanai Y.. Yanaeihara K. Sakai R.
  • Journal Title: American J Pathol 172 Pages: 1729-1739
  • Peer Reviewed
• [Journal Article] CDCP1 regulates peritoneal dissemination of gastric scirrhous carcinoma. (2008)
  • Author(s): Uekita T., Tanaka M., Takigahira M., Miyazawa Y., Kanai Y., Yanagihara K. and Sakai R
  • Journal Title: American Journal of Pathology (in press)
  • Peer Reviewed
• [Journal Article] The C-terminus of ephrin-B1 regulates metalloproteinase secretion and invasion of cancer cells (2007)
  • Author(s): Tanaka M., Sasaki K., Kamata, R., and Sakai R.
  • Journal Title: J. Cell Sci. 120 Pages: 2179-2189
  • Peer Reviewed
• [Journal Article] Phosphorylation of ephrin-B1 regulates dissemination of gastric scirrhous carcinoma (2007)
  • Author(s): Tanaka M., Kamata R., Takigahira M., Yanagihara K. and Sakai R.
  • Journal Title: American Journal of Pathology 171 Pages: 68-78
  • Peer Reviewed
• [Journal Article] Phosphorylation of ephrin-B1 regulates dissemination of gastric scirrhous carcinoma. (2007)
  • Author(s): Tanaka M., Kamata R., Takigahira M., Yanagihara K. and Sakai R.
  • Journal Title: American Joumal of Pathology 171 Pages: 68-78
  • Peer Reviewed
• [Journal Article] The C-terminus of ephrin-B1 regulates metalloproteinase secretion and in vasion of cancer cells. (2007)
  • Author(s): Tanaka M, Sasaki K, Kamata, R. and Sakai R.
  • Journal Title: J Cell Science 120 Pages: 2179-2189
  • Peer Reviewed
• [Presentation] Identification of tyrosine phosphorylated proteins binding to Src family kinases in gastric scirrhous carcinoma (2008)
  • Author(s): Tanaka M., Kamata R., Sasaki K., Sakai R
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] スキルス型癌の間質浸潤におけるリン酸化蛋白質の解析 (2008)
  • Author(s): 田中正光、鎌田礼子、堺隆一
  • Organizer: 第97回日本病理学術総会
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 2008-05-16
• [Presentation] 分子標的としてのephrin-B1信号伝達 (2007)
  • Author(s): 田中正光、鎌田礼子、堺隆一
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ
  • Year and Date: 2007-10-05
• [Presentation] CDCP1はスキルス胃癌の腹膜播種の制御に関与する因子である (2007)
  • Author(s): 上北尚正、田中正光、柳原五吉、堺隆一
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Ephrin-B1 as a therapeutic target of cancer invasion (2007)
  • Author(s): Tanaka M., and Sakai R.
  • Organizer: Mechanisms and Models of cancer
  • Place of Presentation: Salk Institute, La Jolla, USA
  • Year and Date: 2007-08-10
• [Presentation] Ephrin-B1 as a therapeutic target of cancer invasion (2007)
  • Author(s): Tanaka M., and Sakai R
  • Organizer: Mechanisms and Models of Cancer
  • Place of Presentation: Salk Institute,La Jolla,USA
  • Year and Date: 2007-08-10