Irradiated fibroblast-induced bystander effects on the apoptosis, growth and invasive of urothelial carcinoma under cancer–stromal cell interaction

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09138
• 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: Saga University
• Principal Investigator: MAKI KAWASAKI 佐賀大学, 医学部, 助教 (00448474)
• Co-Investigator(Kenkyū-buntansha): 野口 満 佐賀大学, 医学部, 教授 (00325648) ; 東武 昇平 佐賀大学, 医学部, 准教授 (50647021)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: bystander effect / 膀胱癌 / 間質細胞 / 脂肪組織由来間質細胞 / 癌ー間質相互作用

Outline of Final Research Achievements

Irradiated adipose tissue stromal cells (ATSCs) significantly inhibited the growth and promoted apoptosis of non-muscle invasive bladder cancer (NMIBC) than that of ATSCs. In contrast, irradiated ATSCs inhibited growth of muscle invasive bladder cancer (MIBC) than that of ATSCs. Irradiated ATSCs promoted the invasion of MIBC. 53BP1 translocation into the nucleus was observed due to the bystander effect in bladder cancer. Irradiated ATSCs controlled the expression of　extracellular signal-regulated kinase 1/2, p38, Akt in UC. IIrradiated ATSCs promotes invasion and inhibited growth of MIBC, in contrast that inhibited the growth of NMIBC by MAPK molecules mediated bystander mechanism. Our alternative culture model may provide a promising tool for the further radiation therapy into many types of cancer.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

筋層浸潤性膀胱癌の一般的な治療法は、膀胱全摘術と尿路変更術、抗癌剤や放射線治療である。近年、高齢化社会に伴い手術が困難な局所の浸潤・転移を伴う症例や、根治術に耐えられない全身状態の高齢者患者が増加しており、治療法に苦慮している。腎機能障害のため化学療法や放射線療法が十分に施行できない症例もある。最近、PD1抗体などの免疫治療薬と放射線療法併用療法の治験が開始されている。今回、我々が確立した膀胱癌ー放射線被曝間質細胞モデルは、シンプルかつ明瞭解析可能なモデルであり、薬剤投与を行い薬剤耐性・治療効果判定などに応用できる可能性が高いと考える。