Analysis of synovial sarcoma stem cell

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07441
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Hokkaido University
• Principal Investigator: Kimura Taichi 北海道大学, 医学研究院, 客員研究員 (90435959)
• Co-Investigator(Kenkyū-buntansha): 津田 真寿美 北海道大学, 医学研究院, 准教授 (30431307)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 癌幹細胞 / 滑膜肉腫 / 稀少癌

Outline of Final Research Achievements

When we searched for genes whose expression is specifically regulated in synovial sarcoma stem cells, ASCL2 and FOXD3 were found to be up-regulated only in the stem cell culture group, depending on the expression of SS18-SSX2. While the expression of stemness genes such as NANOG, OCT3/4 and SOX2 was decreased, it was revealed that they were not directly involved in the expression of SS18-SSX. In addition, knockdown of PARP1, which was suggested to bind to SS18-SSX in a stem cell-specific manner, was suggested to suppress cell proliferation only under stem cell culture conditions. We aim to develop a novel therapeutic method specific to synovial sarcoma stem cells by advancing more detailed analysis of these genes and binding proteins.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

滑膜肉腫幹細胞に関する知見は少なく、特にマーカーに関しては我々が同定したCXCR4が世界初である。滑膜肉腫幹細胞特異的なSS18-SSX 結合分子及び転写メカニズムの解析には比較・検証対象として滑膜肉腫幹細胞の同定が必須のため独自性が高いと考える。また滑膜肉腫には有効かつ統一された化学療法のレジメンが存在しない。本研究にて新規治療標的を同定し得た場合、再発症例や予後不良例に関しても幅広い治療の選択肢を提供できる。また滑膜肉腫は診断が困難であり確定診断にはキメラ遺伝子の証明が必要となる。本研究により滑膜肉腫幹細胞特異的な分子を同定し得た場合、免疫染色による有用な診断マーカーの開発が可能となる。