Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma
Abstract The purpose of this study is to clarify the metabolic dependence of ovarian clear cell carcinoma (CCC) by comparing normal tissues and to examine the applicability of fluorescence imaging probe to exploit these metabolic differences. Enhanced glutathione synthesis was supported by the incre...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-47637-0 |
| _version_ | 1827634708758921216 |
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| author | Saki Tsuchimochi Osamu Wada-Hiraike Yasuteru Urano Asako Kukita Kohei Yamaguchi Harunori Honjo Ayumi Taguchi Michihiro Tanikawa Kenbun Sone Mayuyo Mori-Uchino Tetsushi Tsuruga Katsutoshi Oda Yutaka Osuga |
| author_facet | Saki Tsuchimochi Osamu Wada-Hiraike Yasuteru Urano Asako Kukita Kohei Yamaguchi Harunori Honjo Ayumi Taguchi Michihiro Tanikawa Kenbun Sone Mayuyo Mori-Uchino Tetsushi Tsuruga Katsutoshi Oda Yutaka Osuga |
| author_sort | Saki Tsuchimochi |
| collection | DOAJ |
| description | Abstract The purpose of this study is to clarify the metabolic dependence of ovarian clear cell carcinoma (CCC) by comparing normal tissues and to examine the applicability of fluorescence imaging probe to exploit these metabolic differences. Enhanced glutathione synthesis was supported by the increased uptake of related metabolites and elevated expression levels of genes. Accumulation of intracellular iron and lipid peroxide, induction of cell death by inhibition of the glutathione synthesis pathway indicated that ferroptosis was induced. The activation of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent imaging probe that recognizes γ-glutamyl transferase, which is essential for the synthesis of glutathione, was investigated in fresh-frozen surgical specimens. gGlu-HMRG detected extremely strong fluorescent signals in the tumor lesions of CCC patients, compared to normal ovaries or endometrium. These results revealed that CCC occurs in the stressful and unique environment of free radical-rich endometrioma, and that glutathione metabolism is enhanced as an adaptation to oxidative stress. Furthermore, a modality that exploits these metabolic differences would be useful for distinguishing between CCC and normal tissues. |
| first_indexed | 2024-03-09T15:17:07Z |
| format | Article |
| id | doaj.art-f0b061a7cb8046fa8e6da9b19b959fd8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:17:07Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f0b061a7cb8046fa8e6da9b19b959fd82023-11-26T13:02:42ZengNature PortfolioScientific Reports2045-23222023-11-0113111210.1038/s41598-023-47637-0Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinomaSaki Tsuchimochi0Osamu Wada-Hiraike1Yasuteru Urano2Asako Kukita3Kohei Yamaguchi4Harunori Honjo5Ayumi Taguchi6Michihiro Tanikawa7Kenbun Sone8Mayuyo Mori-Uchino9Tetsushi Tsuruga10Katsutoshi Oda11Yutaka Osuga12Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoGraduate School of Pharmaceutical Sciences, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoDepartment of Integrated Genomics, Graduate School of Medicine, The University of TokyoDepartment of Obstetrics and Gynecology, Graduate School of Medicine, The University of TokyoAbstract The purpose of this study is to clarify the metabolic dependence of ovarian clear cell carcinoma (CCC) by comparing normal tissues and to examine the applicability of fluorescence imaging probe to exploit these metabolic differences. Enhanced glutathione synthesis was supported by the increased uptake of related metabolites and elevated expression levels of genes. Accumulation of intracellular iron and lipid peroxide, induction of cell death by inhibition of the glutathione synthesis pathway indicated that ferroptosis was induced. The activation of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent imaging probe that recognizes γ-glutamyl transferase, which is essential for the synthesis of glutathione, was investigated in fresh-frozen surgical specimens. gGlu-HMRG detected extremely strong fluorescent signals in the tumor lesions of CCC patients, compared to normal ovaries or endometrium. These results revealed that CCC occurs in the stressful and unique environment of free radical-rich endometrioma, and that glutathione metabolism is enhanced as an adaptation to oxidative stress. Furthermore, a modality that exploits these metabolic differences would be useful for distinguishing between CCC and normal tissues.https://doi.org/10.1038/s41598-023-47637-0 |
| spellingShingle | Saki Tsuchimochi Osamu Wada-Hiraike Yasuteru Urano Asako Kukita Kohei Yamaguchi Harunori Honjo Ayumi Taguchi Michihiro Tanikawa Kenbun Sone Mayuyo Mori-Uchino Tetsushi Tsuruga Katsutoshi Oda Yutaka Osuga Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma Scientific Reports |
| title | Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma |
| title_full | Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma |
| title_fullStr | Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma |
| title_full_unstemmed | Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma |
| title_short | Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma |
| title_sort | characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma |
| url | https://doi.org/10.1038/s41598-023-47637-0 |
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