Analysis of cancer-associated fibroblasts from the perspective of proteinases and epigenetics

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08719
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: SHIMODA MASAYUKI 慶應義塾大学, 医学部(信濃町), 講師 (70383734)
• Co-Investigator(Kenkyū-buntansha): 大塚 崇 東京慈恵会医科大学, 医学部, 教授 (40306717)
• Research Collaborator: KANAI Yae ; OKADA Yasunori
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: がん / 線維芽細胞 / 腫瘍間質 / 網羅的解析 / プロテアーゼ

Outline of Final Research Achievements

Cancer-associated fibroblasts (CAFs) within the tumor stroma are known to acquire activated phenotype and have been shown to stimulate tumor cell proliferation, elevate tumor cell invasion and boost angiogenesis. However, CAFs are also thought to derive from multiple origins and make up a heterogeneous population of cells, it is an important question to understand the unique roles of the different subpopulations of CAFs. In this project, we evaluated various CAF lines by analyzing both their biological tumor-promoting properties and gene expression patterns and sought to identify gene signatures characterizing functionally active CAFs. In these analyses, we identified several genes related to cancer progression increased in functionally active CAFs which would be useful for understanding molecular pathways induced in CAFs. Stromal cell-derived proteinases are also involved in tumor progression and might be potential targets for cancer therapy.

Free Research Field

実験・人体病理学

Academic Significance and Societal Importance of the Research Achievements

CAFは腫瘍進展を手助けするとともに治療に対する抵抗性を強めることから、今後の新たな治療標的の一つとして注目されているものの、CAFは様々な細胞に由来しその多様性から具体的な治療法の確立に至っていないのが現状である。本研究で得られる成果は、生物学的に意義のあるCAF細胞集団を同定しその性質を明らかにすることで、CAFを標的とした新規治療法や機能的分子病理診断の開発に貢献する可能性があると考えている。