Novel ex vivo disease model for extramammary Paget's disease using the cancer tissue-originated spheroid method
Novel ex vivo disease model for extramammary Paget's disease using the cancer tissue-originated spheroid method
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DOI：
10.1016/j.jdermsci.2020.07.006
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发表时间：
2020-09-01
影响因子：
4.6
通讯作者：
Asai, Jun
中科院分区：
文献类型：
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作者：
Arita, Takahiro;Kondo, Jumpei;Asai, Jun
背景：乳房外佩吉特病（EMPD）是一种罕见的皮肤癌，好发于老年人的肛门生殖器部位。转移性EMPD患者的预后很差，因为EMPD治疗近年来进展不大，主要是因为没有EMPD细胞系已established.Objective：我们的目的是建立一个离体EMPD疾病模型，使用癌组织来源的球体（CTOS）方法，这是用来制备和培养原代癌细胞，同时保持细胞-细胞接触。采用CTOS法制备和培养CTOS。对CTOS进行组织学检查。我们研究了CTOS生长的最佳培养基条件和生长因子的影响。结果：成功制备了3个原发灶和2个转移淋巴结的CTOS。其中，2个CTOS（EMPD-3和EMPD-4）可以离体长期维持和传代。将CTOS移植到NOD/Scid小鼠后，CTOS衍生的异种肿瘤表现出导管形成，表明CTOS保留了原始肿瘤特征。化学敏感性试验显示，多西他赛以剂量依赖性方式显著抑制EMPD-3生长，而EMPD-4没有明显抑制。这些研究结果表明EMPD的异质性和潜在的使用化疗敏感性测定与患者衍生的CTOS选择最有效的药物为每个patient.Conclusion：据我们所知，这项研究代表了第一次建立一个体外EMPD疾病模型，涉及传统的细胞系。EMPD CTOS可能有助于开发新的治疗策略。(C)2020日本皮肤病研究学会。Elsevier B.V.出版，保留所有权利。
Background: Extramammary Paget's disease (EMPD) is a rare skin cancer that frequently occurs in the anogenital region in the elderly. Prognosis in patients with metastatic EMPD is poor as EMPD treatment has advanced little in recent years, primarily because no EMPD cell line has been established.Objective: We aimed to establish an ex vivo EMPD disease model using the cancer tissue-originated spheroid (CTOS) method, which is used to prepare and culture primary cancer cells while maintaining cell-cell contact.Methods: Thirteen samples from 12 EMPD patients were obtained. CTOSs were prepared and cultured using CTOS method. Histopathological examination of the CTOSs was performed. We investigated optimum medium conditions and effects of growth factors for CTOS growth. Chemo-sensitivity assays were conducted.Results: CTOSs were successfully prepared from 3 primary lesions and 2 metastatic lymph nodes. Of these, 2 CTOSs (EMPD-3 and EMPD-4) could be maintained and passaged long term ex vivo. Following transplantation of CTOSs to NOD/Scid mice, CTOS-derived xenotumors exhibited ductal formation, indicating that CTOSs retained the original tumor characteristics. Chemo-sensitivity assays revealed that docetaxel significantly inhibited EMPD-3 growth in a dose-dependent manner, whereas EMPD-4 was not clearly inhibited. These findings indicate the heterogeneity of EMPD and potential use of chemosensitivity assays with patient-derived CTOS to select the most effective drugs for each patient.Conclusion: To our knowledge, this study represents the first establishment of an ex vivo-EMPD disease model involving conventional cell lines. EMPD CTOSs might be useful for developing new therapeutic strategies. (C) 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.