Redox Biology (May 2021)
On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity
- Kazufumi Honda,
- Takako Hishiki,
- Sohei Yamamoto,
- Takehiro Yamamoto,
- Nami Miura,
- Akiko Kubo,
- Mai Itoh,
- Wei-Yu Chen,
- Masashi Takano,
- Tomoyuki Yoshikawa,
- Takahiro Kasamatsu,
- Shinichiro Sonoda,
- Hirotoshi Yoshizawa,
- Seigo Nakamura,
- Yuichiro Itai,
- Megumi Shiota,
- Daisuke Koike,
- Masayuki Naya,
- Noriyo Hayakawa,
- Yoshiko Naito,
- Tomomi Matsuura,
- Keiko Iwaisako,
- Toshihiko Masui,
- Shinji Uemoto,
- Kengo Nagashima,
- Yoshinori Hashimoto,
- Tomohiro Sakuma,
- Osamu Matsubara,
- Wilber Huang,
- Tomoaki Ida,
- Takaaki Akaike,
- Yohei Masugi,
- Michiie Sakamoto,
- Tomoyasu Kato,
- Yoshinori Ino,
- Hiroshi Yoshida,
- Hitoshi Tsuda,
- Nobuyoshi Hiraoka,
- Yasuaki Kabe,
- Makoto Suematsu
Affiliations
- Kazufumi Honda
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Japan; Department of Bioregulation, Graduate School of Medicine, Nippon Medical School, Japan
- Takako Hishiki
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan
- Sohei Yamamoto
- Department of Diagnostic Pathology, Anjo Kosei Hospital, Aichi, Japan
- Takehiro Yamamoto
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan
- Nami Miura
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan; Department of Bioregulation, Graduate School of Medicine, Nippon Medical School, Japan
- Akiko Kubo
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan
- Mai Itoh
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan
- Wei-Yu Chen
- Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Masashi Takano
- Department of Obstetrics and Gynecology, National Defense Medical College, Saitama, Japan
- Tomoyuki Yoshikawa
- Department of Clinical Oncology, National Defense Medical College Hospital, Saitama, Japan
- Takahiro Kasamatsu
- Department of Obstetrics and Gynecology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
- Shinichiro Sonoda
- Frontier Core Technology Laboratories, R&D Management Headquarters, FUJIFILM Corporation, Ashigara-gun, Kanagawa, Japan
- Hirotoshi Yoshizawa
- Frontier Core Technology Laboratories, R&D Management Headquarters, FUJIFILM Corporation, Ashigara-gun, Kanagawa, Japan
- Seigo Nakamura
- Frontier Core Technology Laboratories, R&D Management Headquarters, FUJIFILM Corporation, Ashigara-gun, Kanagawa, Japan
- Yuichiro Itai
- Frontier Core Technology Laboratories, R&D Management Headquarters, FUJIFILM Corporation, Ashigara-gun, Kanagawa, Japan
- Megumi Shiota
- Frontier Core Technology Laboratories, R&D Management Headquarters, FUJIFILM Corporation, Ashigara-gun, Kanagawa, Japan
- Daisuke Koike
- FUJIFILM Business Expert Corporation, Ashigara-gun, Kanagawa, Japan
- Masayuki Naya
- Frontier Core Technology Laboratories, R&D Management Headquarters, FUJIFILM Corporation, Ashigara-gun, Kanagawa, Japan
- Noriyo Hayakawa
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan
- Yoshiko Naito
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan
- Tomomi Matsuura
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan
- Keiko Iwaisako
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, 54 Shogoin kawaracho, Sakyo, Kyoto, Japan; Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe city, Kyoto, Japan
- Toshihiko Masui
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, 54 Shogoin kawaracho, Sakyo, Kyoto, Japan
- Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, 54 Shogoin kawaracho, Sakyo, Kyoto, Japan
- Kengo Nagashima
- Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics, Tokyo, Japan
- Yoshinori Hashimoto
- Scientific Imaging Scanner Department, System Division, Hamamatsu Photonics, Hamamatsu, Japan
- Tomohiro Sakuma
- Bioscience Division, Mitsui Knowledge Industry Corporation, Ltd., Tokyo, Japan
- Osamu Matsubara
- Department of Pathology, Hiratsuka Kyosai Hospital, The Cancer Institute, Kanagawa, Japan
- Wilber Huang
- Abnova Corporation, Taipei, Taiwan
- Tomoaki Ida
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
- Takaaki Akaike
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
- Yohei Masugi
- Department of Pathology, Keio University School of Medicine, Japan
- Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Japan
- Tomoyasu Kato
- Division of Gynecology, National Cancer Center Hospital, Tokyo, Japan
- Yoshinori Ino
- Division of Molecular Pathology, National Cancer Center Research Institute, Japan
- Hiroshi Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
- Hitoshi Tsuda
- Department of Basic Pathology, National Defense Medical College, Saitama, Japan
- Nobuyoshi Hiraoka
- Division of Molecular Pathology, National Cancer Center Research Institute, Japan; Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
- Yasuaki Kabe
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Japan
- Makoto Suematsu
- Department Biochemistry, Keio University School of Medicine, Tokyo, Japan; Corresponding author. Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
- Journal volume & issue
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Vol. 41
p. 101926
Abstract
Chemosensitivity to cisplatin derivatives varies among individual patients with intractable malignancies including ovarian cancer, while how to unlock the resistance remain unknown. Ovarian cancer tissues were collected the debulking surgery in discovery- (n = 135) and validation- (n = 47) cohorts, to be analyzed with high-throughput automated immunohistochemistry which identified cystathionine γ-lyase (CSE) as an independent marker distinguishing non-responders from responders to post-operative platinum-based chemotherapy. We aimed to identify CSE-derived metabolites responsible for chemoresistant mechanisms: gold-nanoparticle (AuN)-based surface-enhanced Raman spectroscopy (SERS) was used to enhance electromagnetic fields which enabled to visualize multiple sulfur-containing metabolites through detecting scattering light from Au–S vibration two-dimensionally. Clear cell carcinoma (CCC) who turned out less sensitive to cisplatin than serous adenocarcinoma was classified into two groups by the intensities of SERS intensities at 480 cm−1; patients with greater intensities displayed the shorter overall survival after the debulking surgery. The SERS signals were eliminated by topically applied monobromobimane that breaks sulfane-sulfur bonds of polysulfides to result in formation of sulfodibimane which was detected at 580 cm−1, manifesting the presence of polysulfides in cancer tissues. CCC-derived cancer cell lines in culture were resistant against cisplatin, but treatment with ambroxol, an expectorant degrading polysulfides, renders the cells CDDP-susceptible. Co-administration of ambroxol with cisplatin significantly suppressed growth of cancer xenografts in nude mice. Furthermore, polysulfides, but neither glutathione nor hypotaurine, attenuated cisplatin-induced disturbance of DNA supercoiling. Polysulfide detection by on-tissue SERS thus enables to predict prognosis of cisplatin-based chemotherapy. The current findings suggest polysulfide degradation as a stratagem unlocking cisplatin chemoresistance.
