| Project/Area Number |
20K09553
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56030:Urology-related
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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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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | mesenchymal stem cells / renal cell carcinoma / β-catenin / invasion / migration / 腎細胞癌 / 脂肪由来幹細胞 / βカテニン / PI-3K / 腫瘍微小環境 / drug repositioning |
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| Outline of Research at the Start |
本研究では新たなアプローチとして腎周囲脂肪に存在する脂肪由来幹細胞（ADSC）に着目した。ADSCは腫瘍の微小環境を構成する間葉細胞を供給し、腫瘍の形成や進展に関わるが、RCCにおける役割はほとんど知られていない。一方、幹細胞に対するいくつかの薬剤は、すでに他疾患で治療薬として使用されており、もし、ADSCが標的となるのであれば、新規薬剤を開発せずに治療が可能になる（drug repositioning）。すなわち、本研究では、RCCにおけるADSCの役割を明らかにし、早期に臨床応用が可能な治療法の開発を目指す。
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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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