Mathematical analysis of the mechanism of cancer initiation with the aging of stem cells

2018 Fiscal Year Final Research Report

• Project Area: Establishing a new paradigm of the pathogenesis of diseases through the understanding of stem cell aging
• Project/Area Number: 26115006
• 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: National Cancer Center Japan (2018); Kyushu University (2014-2017)
• Principal Investigator: HAENO HIROSHI 国立研究開発法人国立がん研究センター, 先端医療開発センター, 特任研究員 (70706754)
• Project Period (FY): 2014-07-10 – 2019-03-31
• Keywords: 数理モデル / 確率過程 / シミュレーション解析

Outline of Final Research Achievements

We constructed a mathematical model of a hierarchical tissue from a stem cell population to functional cell populations. By performing comprehensive stochastic simulations, the process of cancer initiation through the tissue collapse was thoroughly investigated. We also obtained experimental data about tissue kinetics of hematopoietic tissue and colon tissue, and incorporated them to the model. As a result, we found that when the number and the cell division rate of a stem cell population is small and low, respectively, the time until cancer initiation becomes long. Finally we revealed the relationship between the complexity of a tissue and the feasibility of cancer initiation.

Free Research Field

数理生物学

Academic Significance and Societal Importance of the Research Achievements

老化関連疾患としてのがんについて、組織構造と発症のし易さの関係性を明らかにすることができた。このことによって、組織ごとに、加齢による細胞の代謝（入れ替わり）の変化と発がんリスクの関係を予測し、予防的措置を講じる必要性や最適な治療標的を示すことで、発症率の減少や治療奏功率の上昇に役立つことが期待される。また、疾患の数理モデル研究の特集雑誌が日本で出版され始め、多くの特集に執筆を行うことで、ゲノム解析・細胞培養実験と合わせた数理モデル研究が注目を浴びることに貢献した。