The role of exosome in the crosstalk between cancer cells and fibroblast

• Project/Area Number: 15K19326
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: Hayashi Yoshito 大阪大学, 医学系研究科, 助教 (80647123)
• Project Period (FY): 2015-04-01 – 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 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 癌関連線維芽細胞 / 癌微小環境

Outline of Final Research Achievements

The present study aimed to reveal the mechanism of the activation of fibrobaslts by cancer cells and the role of cancer-derived exosomes as the communication tool between cancer cells and fibroblasts. We studied the effect of co-existence of cancer cells and fibroblasts using cell lines and nude mice. It is indicated that p53 deficiency played a pivotal role in activation of fibroblast to produce VEGF via ROS production, resulting in tumor progression. We detected the microRNAs in the cancer-derived exosome which activated fibroblasts. These raise the possibility of the cancer-drived exosome as the novel therapeutic target or the useful biomarker.

Research Products

• [Journal Article] p53 functional deficiency in human colon cancer cells promotes fibroblast-mediated angiogenesis and tumor growth. (2016)
  • Author(s): Hayashi Y, Tsujii M, Kodama T, Akasaka T, Kondo J, Hikita H, Inoue T, Tsujii Y, Maekawa A, Yoshii S, Shinzaki S, Watabe K, Tomita Y, Inoue M, Tatsumi T, Iijima H, Takehara T.
  • Journal Title: Carcinogenesis. Volume: 37 Issue: 10 Pages: 972-984
  • DOI: 10.1093/carcin/bgw085
  • Peer Reviewed
• [Presentation] Exosomes derived from colon cancer cells promote tumor progression via the activation of fibroblasts in tumor microenvironment. (2017)
  • Author(s): Yoshito Hayashi, Shunsuke Yoshii, Yoshiki Tsujii, Takanori Inoue, Keiichi Kimura, Akihiko Sakatani, Kengo Nagai, Tetsuji Fujinaga, Satoshi Hiyama, Shinichiro Shinzaki, Kenji Watabe, Hideki Iijima, Tetsuo Takehara
  • Organizer: Digestive Disease Week 2017
  • Place of Presentation: Chicago
  • Year and Date: 2017-05-07
  • Int'l Joint Research
• [Presentation] IL-11 from fibroblasts enhances tumor progression in colon cancer microenvironment (2016)
  • Author(s): Yoshito Hayashi, Takanori Inoue, Keiichi Kimura, Hayato Hikita, Minoru Shigekawa, Ryotaro Sakamori, Tomohide Tatsumi, and Tetsuo Takehara
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-07
• [Presentation] p53機能欠損大腸癌の癌微小環境におけるVEGFの役割 (2016)
  • Author(s): 林義人、辻井正彦、竹原徹郎
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-23
• [Presentation] p53機能不全大腸癌の癌微小環境におけるVEGFの役割 (2016)
  • Author(s): 林義人、辻井正彦、竹原徹郎
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-23