S100 protein in metastasis and dormancy of breast cancer stem cell

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23900
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Fujita Health University
• Principal Investigator: Watanabe Takashi 藤田医科大学, 医学部, 講師 (10402562)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: がん幹細胞 / 乳がん / S100A10 / 肝転移

Outline of Final Research Achievements

Cancer cells with cancer stem cell (CSC) properties drive initiation and growth of metastases at distant sites. We have established the breast cancer patient-derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, the expression levels of S100A10 was much higher in the CD44+ cancer cells metastasized to the liver. Knockdown of S100A10 in breast cancer cells suppressed and overexpression of S100A10 in breast cancer PDX cells enhanced their invasion abilities and 3D organoid formation capacities in vitro. Mechanistically, S100A10 regulated the matrix metalloproteinase activity and the expression levels of stem cell-related genes. Finally, knockdown of S100A10 significantly reduced their metastatic ability to the liver in vivo. These findings suggest that S100A10 functions as a metastasis promoter of breast CSCs by conferring both invasion ability and CSC properties in breast cancers.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

我々はS100A10が転移がん幹細胞で特異的に発現し、転移の超早期段階から発現していることを見出し、S100A10がどのように転移がん幹細胞の性質や転移能を調節しているか明らかにした。本研究は転移乳がん細胞の「がん幹細胞」としての性質の維持と「超早期」の転移巣での生存を制御する分子機構を解明した点で学術的意義が大きい。また、公共データベースでの解析によりS100A10の発現レベルと全生存期間との関係には負の相関が認められるため、原発巣でのS100A10の発現が予後を規定する因子、病理診断マーカーとなる可能性がある。今後、本研究成果を元に応用研究が進むことを期待している。