Endothelial Stem Cell System in the Tumor Vasculature

• Project/Area Number: 15K18409
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Osaka University
• Principal Investigator: Naito Hisamichi 大阪大学, 微生物病研究所, 助教 (30570676)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍血管 / 血管内皮幹細胞 / 薬剤耐性 / 血管新生 / SP細胞 / 血管内皮細胞

Outline of Final Research Achievements

We have been studying the endothelial stem cell system in the vasculature. Here we identified this endothelial stem cell system in the tumor vasculature. In the tumor vasculature, the percentage of endothelial stem cells was significantly increased compared to normal tissue. Moreover, we showed endothelial hierarchy by transplantation model. By gene expression analysis, we found that endothelial stem cell in the tumor highly express drug resistance genes. Addition of an inhibitor which blocks the function of drug resistance protein inhibited the colony formation of endothelial stem cells. Furthermore, administration of this inhibitor to the tumor bearing mice induced regression of tumor size of these mice. Our results suggest the existence of endothelial hierarchy system in the tumor vasculature. Targeting this system may be a promising therapeutic target in the future.

Research Products

• [Journal Article] Plakoglobin maintains the integrity of vascular endothelial cell junctions and regulates VEGF-induced phosphorylation of VE-cadherin. (2017)
  • Author(s): Muramatsu F, Kidoya H, Naito H, Hayashi Y, Iba T, Takakura N
  • Journal Title: J Biochem Volume: 印刷中 Issue: 1 Pages: 55-62
  • DOI: 10.1093/jb/mvx001
  • NAID: 40021274631
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Endothelial side population cells contribute to Tumor angiogenesis and antiangiogenic drug resistance. (2016)
  • Author(s): Naito H, Wakabayashi T, Kidoya H, Muramatsu F, Takara K, Eino D, Yamane K, Iba T, Takakura N
  • Journal Title: Cancer Research Volume: 76 Issue: 11 Pages: 3200-3210
  • DOI: 10.1158/0008-5472.can-15-2998
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] PSF1 (Partner of SLD Five 1) is a Prognostic Biomarker in Patients with Non-small Cell Lung Cancer Treated with Surgery Following Preoperative Chemotherapy or Chemoradiotherapy. (2016)
  • Author(s): Kanzaki R, Naito H, Kise K, Takara K, Eino D, Minami M, Shintani Y, Funaki S, Kawamura T, Kimura T, Okumura M, Takakura N.
  • Journal Title: Ann Surg Oncol. Volume: Nov;23(12) Pages: 4093-4100
  • Peer Reviewed
• [Journal Article] Regulation of SLD5 gene expression by miR-370 during acute growth of cancer cells. (2016)
  • Author(s): Yamane K, Naito H, Wakabayashi T, Yoshida H, Muramatsu F, Iba T, Kidoya H, Takakura N
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 30941-30941
  • DOI: 10.1038/srep30941
  • NAID: 120007096890
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Endothelial Side Population Cells Contribute to Tumor Angiogenesis and Antiangiogenic Drug Resistance (2016)
  • Author(s): Hisamichi Naito, Taku Wakabayashi, Hiroyasu Kidoya, Fumitaka Muramatsu, Kazuhiro Takara, Daisuke Eino, Keitaro Yamane, Tomohiro Iba, and Nobuyuki Takakura
  • Journal Title: Cancer Research Volume: -
  • Peer Reviewed / Acknowledgement Compliant
• [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] Endothelial side population cells contribute to tumor angiogenesis (2016)
  • Author(s): Hisamichi Naito
  • Organizer: 19th International Vascular biology meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-10-30
  • Int'l Joint Research
• [Presentation] Inhibition of TNF mediated apoptosis is an indispensable mechanism for survival of EC in adult mice (2016)
  • Author(s): Hisamichi Naito
  • Organizer: Gordon Research Conference
  • Place of Presentation: Girona, Spain
  • Year and Date: 2016-07-17
  • Int'l Joint Research
• [Presentation] リゾリン脂質による新たな腫瘍血管制御法の開発 (2015)
  • Author(s): 髙良 和宏、内藤 尚道、若林 卓、永野 大輔、村松 史隆、木戸屋 浩康、大戸 貴代、安田 大恭、石井 聡、安藤 康史、福原 茂朋、望月 直樹、高倉 伸幸
  • Organizer: CVMW2015 心血管代謝週間
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-10
• [Presentation] 腫瘍血管新生におけるmiR-125bの機能解析 (2015)
  • Author(s): 村松 史隆、木戸屋 浩康、内藤 尚道、高倉 伸幸
  • Organizer: CVMW2015 心血管代謝週間
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-10
• [Presentation] The role of vascular resident endothelial stem/progenitor cells in pathophysiological angiogenesis. (2015)
  • Author(s): Hisamichi Naito
  • Organizer: Asia-Australia Vascular Biology
  • Place of Presentation: Busan, Korea
  • Year and Date: 2015-10-17
  • Int'l Joint Research / Invited
• [Presentation] Tumor vascular normalization by LPA (2015)
  • Author(s): Kazuhiro Takara, Hisamichi Naito, Taku Wakabayashi, Daisuke Eino, Fumitaka Muramatsu, Hiroyasu Kidoya, Nobuyuki Takakura
  • Organizer: Metabolism in Cancer and Stromal Cells
  • Place of Presentation: Leuven, Belgium
  • Year and Date: 2015-09-08
  • Int'l Joint Research
• [Remarks] 大阪大学 研究者詳細
  • URL: http://www.dma.jim.osaka-u.ac.jp/view?l=ja&u=6802