Development of the new treatment for thyroid cancer by targeting the plasticity of the cancer stem cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16167
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Nagasaki University
• Principal Investigator: SHIMAMURA Mika 長崎大学, 原爆後障害医療研究所, 助教 (90736406)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 甲状腺癌 / 癌幹細胞

Outline of Final Research Achievements

The existence of cancer stem cells (CSCs) has long been proposed. This project has focused on redox system, especially reactive oxygen species (ROS), as functional marker(s) for thyroid CSCs. The changes in spherogenicity was evaluated by separating the cells into ROShigh vs. ROSlow subfractions, and by altering ROS levels with chemicals. We found that intracellular ROS levels is critical for spherogenicity, indicating the importance of elucidation for mechanisms to keep low ROS levels. ROSlow subfraction had higher intracellular GSH levels and decreased levels of basic/maximum oxidative phosphorylation and glycolysis, compared with ROShigh subfraction, suggesting that ROSlow cells are in quiescent state.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

CSCの同定・解析は、癌の発生原因の解明のみでなく治療開発までの幅広い領域にとって重要な研究である。本研究では、甲状腺癌CSC調節因子として初めてROS・レドックス調節に注目した。さらに甲状腺CSCの可塑性という特徴に注目した研究は他にはない。今回得た結果より癌組織の自己複製と成長の可能性を枯渇させることによって長期的な疾病根絶を達成するためのCSC標的治療の重要性を考えると、ROSは甲状腺癌におけるCSC標的治療のための良い候補であるかもしれない。