Analysis of regulatory mechanism of tumor angiogenesis by Tie1 ectodomain

• Project/Area Number: 26830072
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Osaka University
• Principal Investigator: YAMAKAWA DAISHI 大阪大学, 微生物病研究所, 特任研究員(常勤) (20631097)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腫瘍血管新生 / 血管新生阻害 / 蛋白質分解酵素 / 血管内皮細胞 / Tie1 / Tie2 / 抗腫瘍効果

Outline of Final Research Achievements

Suppression of tumor angiogenesis suppress penetration of nutrients into tumor, resulting in tumor growth suppression. It is known that receptor tyrosine kinase Tie1 associates with vascular stabilization. In this study, we focused on the function of Tie1 ectodomain which is cleaved by angiogenic stimulation. We identified that Tie1 ectodomain suppresses pathological angiogenesis via direct interaction with endothelial cells in vitro and in vivo.
In the future, we hope to establish the induction method of Tie1 ectodomain shedding or regulation method of Tie1 ectodomain binding molecule in tumor vasculature.

Research Products

• [Journal Article] Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy. (2016)
  • Author(s): Zhang L, Takara K, Yamakawa D, Kidoya H, Takakura N.
  • Journal Title: Cancer Sci Volume: 107 Issue: 1 Pages: 36-44
  • DOI: 10.1111/cas.12836
  • Peer Reviewed / Open Access
• [Journal Article] APJ Regulates Parallel Alignment of Arteries and Veins in the Skin. (2015)
  • Author(s): Kidoya H, Naito H, Muramatsu F, Yamakawa D, Jia W, Ikawa M, Sonobe T, Tsuchimochi H, Shirai M, Adams RH, Fukamizu A, Takakura N.
  • Journal Title: Dev Cell. Volume: 33 Issue: 3 Pages: 247-259
  • DOI: 10.1016/j.devcel.2015.02.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 腫瘍血管新生におけるTie1細胞外ドメイン切断の意義 (2016)
  • Author(s): 山川大史
  • Organizer: 第2回血管生物医学会若手研究会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-04
• [Presentation] DNA複製因子PSF1のプロモーター活性を指標とした増殖血管内皮細胞の分離 (2015)
  • Author(s): 山川大史、木戸屋浩康、橘田未来、細島祥子、高倉伸幸
  • Organizer: 第23回日本血管生物医学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-11
• [Presentation] Tie1細胞外ドメインの脱落が腫瘍血管新生を制御する (2015)
  • Author(s): 山川大史、木戸屋浩康、ジャイシン、橘田未来、高倉伸幸
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-09
• [Remarks] 大阪大学 微生物病研究所 情報伝達分野
  • URL: http://st.biken.osaka-u.ac.jp
• [Remarks] 大阪大学微生物病研究所ホームページ
  • URL: http://st.biken.osaka-u.ac.jp
• [Remarks] 大阪大学研究者総覧
  • URL: http://www.dma.jim.osaka-u.ac.jp/view?l=ja&u=3220