Elucidation of the role of adipose-derived stem cells in renal cell carcinoma and development of new therapeutic strategies

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09553
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Akita University
• Principal Investigator: Numakura Kazuyuki 秋田大学, 医学部附属病院, 病院准教授 (90566415)
• 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)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 脂肪由来幹細胞 / 腎細胞癌 / βカテニン / 浸潤

Outline of Final Research Achievements

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.

Free Research Field

腎細胞癌

Academic Significance and Societal Importance of the Research Achievements

β-カテニンを標的とすることで、従来の治療に耐性を示す腎細胞癌の新規治療となる可能性が示された。