A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan
Abstract Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD mod...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84566-y |
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| author | Takamichi Ito Yuka Tanaka Dai Ogata Haruto Nishida Tatsushi Shiomi Ryo Tanaka Aya Kawaguchi Azusa Miyashita Satoshi Fukushima Naoko Shojiguchi Hiroyuki Goto Yaei Togawa Takahiro Kiyohara Yoshinao Oda Takeshi Nakahara |
| author_facet | Takamichi Ito Yuka Tanaka Dai Ogata Haruto Nishida Tatsushi Shiomi Ryo Tanaka Aya Kawaguchi Azusa Miyashita Satoshi Fukushima Naoko Shojiguchi Hiroyuki Goto Yaei Togawa Takahiro Kiyohara Yoshinao Oda Takeshi Nakahara |
| author_sort | Takamichi Ito |
| collection | DOAJ |
| description | Abstract Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD models has hampered investigation of EMPD. Here we investigated whether trophoblast cell surface antigen 2 (TROP2) could be a promising therapeutic target for EMPD. We retrospectively collected 108 samples from 54 patients with primary and metastatic EMPD from 10 Japanese institutions, and compared TROP2 expression between primary and metastatic lesions of each paired sample. In vitro assays were performed using a newly established EMPD cell line, KS-EMPD-1. TROP2 was strongly and homogeneously expressed in patient tissues, regardless of primary or metastatic lesions. The KS-EMPD-1 cells were treated with a TROP2-targeted antibody–drug conjugate (ADC), sacituzumab govitecan, and it significantly reduced cell viability in a dose-dependent manner compared with that of the cells treated with sacituzumab alone. Knockdown of TROP2 reduced cell viability and cell migration, and caused slight upregulation of the apoptosis-related factors, together with downregulation of the epithelial-to-mesenchymal transition-related factors. These findings suggest that a TROP2-targeted ADC may be a promising treatment option for unresectable EMPD. |
| format | Article |
| id | doaj-art-1dc138a505e74b82ac9cb3ce4600a8f0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-1dc138a505e74b82ac9cb3ce4600a8f02025-01-05T12:22:20ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-024-84566-yA multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in JapanTakamichi Ito0Yuka Tanaka1Dai Ogata2Haruto Nishida3Tatsushi Shiomi4Ryo Tanaka5Aya Kawaguchi6Azusa Miyashita7Satoshi Fukushima8Naoko Shojiguchi9Hiroyuki Goto10Yaei Togawa11Takahiro Kiyohara12Yoshinao Oda13Takeshi Nakahara14Department of Dermatology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Dermatology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Dermatologic Oncology, National Cancer Center HospitalDepartment of Diagnostic Pathology, Faculty of Medicine, Oita UniversityDepartment of Pathology, Kawasaki Medical SchoolDepartment of Dermatology, Kawasaki Medical SchoolDepartment of Dermatology, Kurume University School of MedicineDepartment of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto UniversityDepartment of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto UniversityDepartment of Pathology, Saitama Medical University International Medical CenterDepartment of Dermatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Dermatology, Chiba University HospitalDepartment of Dermatology, Kansai Medical University Medical CenterDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Dermatology, Graduate School of Medical Sciences, Kyushu UniversityAbstract Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD models has hampered investigation of EMPD. Here we investigated whether trophoblast cell surface antigen 2 (TROP2) could be a promising therapeutic target for EMPD. We retrospectively collected 108 samples from 54 patients with primary and metastatic EMPD from 10 Japanese institutions, and compared TROP2 expression between primary and metastatic lesions of each paired sample. In vitro assays were performed using a newly established EMPD cell line, KS-EMPD-1. TROP2 was strongly and homogeneously expressed in patient tissues, regardless of primary or metastatic lesions. The KS-EMPD-1 cells were treated with a TROP2-targeted antibody–drug conjugate (ADC), sacituzumab govitecan, and it significantly reduced cell viability in a dose-dependent manner compared with that of the cells treated with sacituzumab alone. Knockdown of TROP2 reduced cell viability and cell migration, and caused slight upregulation of the apoptosis-related factors, together with downregulation of the epithelial-to-mesenchymal transition-related factors. These findings suggest that a TROP2-targeted ADC may be a promising treatment option for unresectable EMPD.https://doi.org/10.1038/s41598-024-84566-yExtramammary Paget diseaseTrophoblast cell surface antigen 2Antibody–drug conjugateSacituzumab govitecan |
| spellingShingle | Takamichi Ito Yuka Tanaka Dai Ogata Haruto Nishida Tatsushi Shiomi Ryo Tanaka Aya Kawaguchi Azusa Miyashita Satoshi Fukushima Naoko Shojiguchi Hiroyuki Goto Yaei Togawa Takahiro Kiyohara Yoshinao Oda Takeshi Nakahara A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan Scientific Reports Extramammary Paget disease Trophoblast cell surface antigen 2 Antibody–drug conjugate Sacituzumab govitecan |
| title | A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan |
| title_full | A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan |
| title_fullStr | A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan |
| title_full_unstemmed | A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan |
| title_short | A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan |
| title_sort | multicenter study on trop2 as a potential targeted therapy for extramammary paget disease in japan |
| topic | Extramammary Paget disease Trophoblast cell surface antigen 2 Antibody–drug conjugate Sacituzumab govitecan |
| url | https://doi.org/10.1038/s41598-024-84566-y |
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