Explication of a tumor angiogenesis mechanism through in vivo imaging of VEGF molecule

• Project/Area Number: 17H06838
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Tumor biology
• Research Institution: Osaka University
• Principal Investigator: Muramatsu Fumitaka 大阪大学, 微生物病研究所, 特任研究員 (90803627)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 血管新生 / 生体イメージング / 腫瘍 / 血管内皮細胞 / 腫瘍血管新生 / 癌 / イメージング / 腫瘍血管

Outline of Final Research Achievements

We performed in vivo imaging analysis of a tumor vessel formation through VEGF signal. The efferent angiogenesis was observed among GL261 glioma and LLC lung cancer, in which the vascular endothelial tip cells extended along with tumor tissues infiltrating direction.　These efferent elongation of vascular endothelial tip cells in tumor infiltrating rims were strongly depending on VEGF singals. There was some specific tumor cell group, which shows strong VEGF expression regardless of hypoxia signals, among tumor tissues.　These outcomes invented new schema of tumor angiogenesis.

Academic Significance and Societal Importance of the Research Achievements

腫瘍組織の血管分布は不均一であるがゆえに灌流が悪く、抗がん剤送達の妨げとなっている。これは急速な腫瘍組織の成長と、それに伴い供給される新生血管のミスマッチが原因と考えられているが、どのような法則に基づき血管が分布しているのかはよくわかっていなかった。我々は神経膠腫や肺がん組織などにおける血管新生を生体イメージング解析し、腫瘍組織の血管分布変化を再評価した。その結果、腫瘍内部に存在する血管内皮細胞が、腫瘍組織内を灌流する血管を構成するように遠心性に伸長する性質を有することを明らかとした。この性質を今後さらに調べることで、腫瘍血管制御を介した、新たながん治療の開発につながると期待される。

Research Products

• [Journal Article] CD157 Marks Tissue-Resident Endothelial Stem Cells with Homeostatic and Regenerative Properties. (2018)
  • Author(s): Wakabayashi T, Naito H, Suehiro JI, Lin Y, Kawaji H, Iba T, Kouno T, Ishikawa-Kato S, Furuno M, Takara K, Muramatsu F, Weizhen J, Kidoya H, Ishihara K, Hayashizaki Y, Nishida K, Yoder MC, Takakura N.
  • Journal Title: Cell Stem Cell. Volume: 22 Issue: 3 Pages: 348-397
  • DOI: 10.1016/j.stem.2018.01.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] In vivo Imaging Analysis of Combined Chemotherapy Resistant Glioblastoma Multiforme (2018)
  • Author(s): Fumitaka Muramatsu, Kidoya Hiroyasu, Yohei Tsukada, Yumiko Hayashi, Tomohiro Iba, Hisamichi Naito, Nobuyuki Takakura
  • Organizer: International Vascular Biology Meeting 2018
  • Int'l Joint Research
• [Presentation] 化学療法耐性神経膠芽腫の生体イメージング解析 (2018)
  • Author(s): 村松 史隆, 木戸屋 浩康, 塚田 陽平, 林 弓美子, 高倉 伸幸
  • Organizer: 第26回日本血管生物医学会学術集会
• [Presentation] In vivo Imaging Analysis of Combined Chemotherapy Resistant Glioblastoma (2018)
  • Author(s): Fumitaka Muramatsu, Kidoya Hiroyasu, Yohei Tsukada, Yumiko Hayashi, Tomohiro Iba, Hisamichi Naito, Nobuyuki Takakura
  • Organizer: The 16th Korea-Japan Joint Symposium on Vascular Viology
  • Int'l Joint Research
• [Presentation] In vivo imaging analysis of combined chemotherapy resistant glioblastoma multiforme (2018)
  • Author(s): Fumitaka Muramatsu, Hiroyasu Kidoya, Tsukada Yohei, Yumiko Hayashi, Tomohiro Iba, Hisamichi Naito, Nobuyuki Takakura
  • Organizer: The International Vascular Biology Meeting 2018
  • Int'l Joint Research
• [Presentation] 神経膠芽腫における腫瘍血管新生の生体イメージング解析 (2017)
  • Author(s): 村松 史隆、林 弓美子、塚田 陽平、内藤 尚道、高倉 伸幸
  • Organizer: 第25回日本血管生物医学会学術集会
• [Book] 月刊 細胞 (2018)
  • Author(s): 木戸屋 浩康・村松 史隆
  • Total Pages: 4
  • Publisher: ニューサイエンス社