Ito Takamichi, Tanaka Yuka, Ogata Dai, Nishida Haruto, Shiomi Tatsushi, Tanaka Ryo, Kawaguchi Aya, Miyashita Azusa, Fukushima Satoshi, Shojiguchi Naoko, Goto Hiroyuki, Togawa Yaei, Kiyohara Takahiro, Oda Yoshinao, Nakahara Takeshi
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan.
Sci Rep. 2025 Jan 2;15(1):409. doi: 10.1038/s41598-024-84566-y.
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.
乳腺外佩吉特病（EMPD）是一种罕见的皮肤癌，通常发生在老年人的肛门生殖器区域。由于转移性或不可切除性EMPD的治疗效果仍然较差，因此迫切需要开发新的治疗方法。然而，EMPD模型的缺乏阻碍了对EMPD的研究。在此，我们研究了滋养层细胞表面抗原2（TROP2）是否可能成为EMPD的一个有前景的治疗靶点。我们回顾性收集了来自日本10家机构的54例原发性和转移性EMPD患者的108份样本，并比较了每对样本中原发性和转移性病变之间的TROP2表达。使用新建立的EMPD细胞系KS-EMPD-1进行了体外试验。TROP2在患者组织中强烈且均匀地表达，无论原发性或转移性病变如何。用靶向TROP2的抗体药物偶联物（ADC）戈沙妥珠单抗处理KS-EMPD-1细胞，与单独用戈沙妥珠单抗处理的细胞相比，它以剂量依赖的方式显著降低了细胞活力。敲低TROP2降低了细胞活力和细胞迁移，并导致凋亡相关因子略有上调，同时上皮-间质转化相关因子下调。这些发现表明，靶向TROP2的ADC可能是不可切除性EMPD的一种有前景的治疗选择。
