2023 Fiscal Year Annual Research Report
腎細胞癌における脂肪由来幹細胞の役割の解明と新たな治療戦略の開発
| Project/Area Number |
20K09553
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| Research Institution | Akita University |
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Principal Investigator |
沼倉 一幸 秋田大学, 医学部附属病院, 講師 (90566415)
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| Co-Investigator(Kenkyū-buntansha) |
明石 英雄 秋田大学, 医学系研究科, 助教 (10431785)
小林 瑞貴 秋田大学, 医学部附属病院, 助教 (20838627)
武藤 弓奈 秋田大学, 医学部附属病院, 医員 (60837706)
松峯 元 東京女子医科大学, 医学部, 准教授 (80598144)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | mesenchymal stem cells / renal cell carcinoma / β-catenin / invasion / migration |
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| Outline of Annual Research Achievements |
Adipose-derived mesenchymal stem cells (A-MSCs) are recognized as key components of the tumor microenvironment. However, their specific involvement in renal cell carcinoma (RCC) progression remains largely unknown. This study aims to elucidate the role of A-MSCs in RCC.
A-MSCs exhibited multipotency, capable of differentiating into adipocytes, chondroblasts, and osteoblasts. R-MSCs showed enhanced mRNA expression of Hes1, Hey1, and Twist, along with increased β-catenin protein levels and decreased phospho-Akt (Ser473) and phospho-p38 MAPK compared to D-MSCs, indicating reduced stem cell potential via molecular pathways. This was further corroborated by aldehyde dehydrogenase enzymatic activity (ALDH) assays, revealing fewer ALDH+ cells in R-MSCs than in D-MSCs. Co-culturing with RCC cell lines demonstrated increased migration with R-MSCs compared to D-MSCs. Pathway analysis revealed elevated CD44 mRNA expression in RCC cell lines co-cultured with R-MSCs. IHC staining of β-catenin in perirenal stromal tissue from RCC surgical specimens revealed a higher positive score correlating with tumor aggressiveness.
Co-culture with R-MSCs intensified tumor invasiveness, suggesting a role in promoting A-MSC differentiation and facilitating RCC migration and invasion via the Wnt/β-catenin pathway. This underscores the significance of A-MSCs in the RCC microenvironment and their potential as therapeutic targets.
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