Roles of tumor microenvironments in radiotherapy for solid tumors on the basis of cell cycle imaging

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861569
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAIDA Atsushi 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (40632097)
• Co-Investigator(Renkei-kenkyūsha): MIURA Masahiko 東京医科歯科大学, 医歯学総合研究科, 教授 (10272600)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 放射線治療 / 固形腫瘍 / 細胞動態 / Fucci / 腫瘍内微小環境 / G2アレスト

Outline of Final Research Achievements

In this study, we analyzed intratumoral cell cycle kinetics after X-irradiation of tumor xenografts expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci), a novel system to visualize cell cycle kinetics in vivo. Cell cycle kinetics after X-irradiation was examined by using tumor sections and in vivo real-time imaging system in tumor xenografts. We found that G2 arrest was remarkably prolonged, up to 5 days after 10-Gy irradiation, in contrast to monolayer cultures where G2 arrest returned within 24 h. Cells isolated from tumors 5 days after irradiation exhibited a higher surviving fraction than those isolated immediately or one day after irradiation. In this study, we clearly demonstrated unusual post-irradiation cell cycle kinetics in tumor xenografts. Our findings imply that prolonged G2 arrest occurring in tumor microenvironments following irradiation may function as a radioresistance mechanism.

Free Research Field

放射線生物学