Elucidation of dormant cancer stem cells and their niche properties in human solid tumors

2014 Fiscal Year Final Research Report

• Project Area: Development of Novel Treatment Strategies Targeting Cancer Stem Cells
• Project/Area Number: 22130005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TANAKA Shinji 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (30253420)
• Co-Investigator(Kenkyū-buntansha): MORI Masaki 大阪大学, 大学院医学系研究科, 教授 (70190999)
• Co-Investigator(Renkei-kenkyūsha): ISHII Hideshi 大阪大学, 大学院医学系研究科, 特任教授 (10280736)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 癌 / 外科 / 転移 / 再生医学 / トランスレーショナルリサーチ / プロテアソーム / 細胞周期 / 代謝

Outline of Final Research Achievements

Based on the proteasome-independent potentials, human cancer stem cells (CSCs) were visualized and isolated to identify the specific inhibitor combined with conventional anti-cancer drugs. CSCs facilitated metastatic activities with niche formation by recruitment of macrophages in vivo. Additionally, we synthesized the transgenic mice with monitoring of the proteasome activity to reveal in vivo mechanisms of stemness and carcinogenesis of various malignancies including pancreatic cancer.
To characterize the biological significance of the cell cycle phases in CSCs, we used the visualizing system by ‘fluorescence ubiquitin-based cell cycle indicator’ (Fucci). This system allowed the G2M phase as green whereas G1 phase as red colors. We were able to identify therapy-resistant CSCs in G1 phase, although cell mobility and invasion linked with G2M phase. Several genes were characterized and focused on the novel therapeutic targets.

Free Research Field

医歯薬学