Elucidation of oxidative stress resistance mechanisms in head and neck cancer using novel redox-related fluorescent probes

Research Project

Project/Area Number	17K11379
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Otorhinolaryngology
Research Institution	The University of Tokyo
Principal Investigator	Yoshida Masafumi 東京大学, 医学部附属病院, 届出研究員 (80396754)
Project Period (FY)	2017-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	頭頸部外科学 / 蛍光イメージング / 酸化ストレス
Outline of Final Research Achievements	We applied gGlu-HMRG, a probe for detecting GGT activity, to head and neck carcinoma resected specimens, and fluorescence was detected in about half of the specimens. Comprehensive RNA sequencing and pathway analysis of the head and neck cancer resected specimens showed that GGT1, a major subtype of GGT, was highly expressed in about half of the specimens. In the high GGT1 group, FGF21 was highly expressed and PI3K pathway was activated. In addition, GGT1 was highly expressed in Detroit562 cells derived from head and neck cancers, where the PI3K pathway is activated, suggesting a relationship between GGT1 activity and the PI3K pathway.
Academic Significance and Societal Importance of the Research Achievements	当初の目的である頭頸部癌における酸化ストレス耐性機構の解明にまでは至らなかったが、細胞内GSH濃度と関連のあるGGT活性につき、蛍光イメージングの結果からGGT活性とPI3K経路の関連という新たな知見が得られたことは、蛍光イメージングによって同じ頭頸部癌における違う特徴が検出可能であることを示す重要な成果と考えられる。