Identifying high-grade serous ovarian carcinoma–specific extracellular vesicles by polyketone-coated nanowires

Author:

Yokoi Akira123ORCID,Ukai Mayu1ORCID,Yasui Takao4567ORCID,Inokuma Yasuhide3689ORCID,Hyeon-Deuk Kim610ORCID,Matsuzaki Juntaro11ORCID,Yoshida Kosuke12ORCID,Kitagawa Masami112,Chattrairat Kunanon5ORCID,Iida Mikiko5ORCID,Shimada Taisuke5ORCID,Manabe Yumehiro8,Chang I-Ya10ORCID,Asano-Inami Eri112,Koya Yoshihiro112,Nawa Akihiro112,Nakamura Kae113ORCID,Kiyono Tohru14ORCID,Kato Tomoyasu15,Hirakawa Akihiko16,Yoshioka Yusuke17,Ochiya Takahiro17ORCID,Hasegawa Takeshi18ORCID,Baba Yoshinobu5719ORCID,Yamamoto Yusuke20ORCID,Kajiyama Hiroaki11ORCID

Affiliation:

1. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

2. Nagoya University Institute for Advanced Research, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.

3. Japan Science and Technology Agency (JST), FOREST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.

4. Department of Life Science and Technology, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-8501, Japan.

5. Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.

6. Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.

7. Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.

8. Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8 Kita-ku, Sapporo, Hokkaido 060-8628, Japan.

9. Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.

10. Department of Chemistry, Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8502, Japan.

11. Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 2-15-45 Mita, Minato-ku, Tokyo 108-8345, Japan.

12. Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

13. Center for Low-Temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.

14. Project for Prevention of HPV-related Cancer, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.

15. Department of Gynecologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

16. Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

17. Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.

18. Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.

19. Institute of Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Kanagawa, Inage-ku, Chiba, Chiba 263-8555, Japan.

20. Laboratory of Integrative Oncology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Abstract

Cancer cell–derived extracellular vesicles (EVs) have unique protein profiles, making them promising targets as disease biomarkers. High-grade serous ovarian carcinoma (HGSOC) is the deadly subtype of epithelial ovarian cancer, and we aimed to identify HGSOC-specific membrane proteins. Small EVs (sEVs) and medium/large EVs (m/lEVs) from cell lines or patient serum and ascites were analyzed by LC-MS/MS, revealing that both EV subtypes had unique proteomic characteristics. Multivalidation steps identified FRα, Claudin-3, and TACSTD2 as HGSOC-specific sEV proteins, but m/lEV-associated candidates were not identified. In addition, for using a simple-to-use microfluidic device for EV isolation, polyketone-coated nanowires (pNWs) were developed, which efficiently purify sEVs from biofluids. Multiplexed array assays of sEVs isolated by pNW showed specific detectability in cancer patients and predicted clinical status. In summary, the HGSOC-specific marker detection by pNW are a promising platform as clinical biomarkers, and these insights provide detailed proteomic aspects of diverse EVs in HGSOC patients.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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