Novel ex vivo disease model for extramammary Paget's disease using the cancer tissue-originated spheroid method
| Autor: | Jun Asai, Yuka Kaneko, Yukiyasu Arakawa, Masahiro Inoue, Mari Matsui, Jumpei Kondo, Miho Tsutsumi, Norito Katoh, Mai Kanemaru, Takahiro Arita |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Skin Neoplasms Primary Cell Culture Antineoplastic Agents Dermatology Disease Docetaxel Biochemistry Extramammary Paget's disease 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Spheroids Cellular medicine Tumor Cells Cultured Humans Molecular Biology Penile Neoplasms Aged Aged 80 and over Dose-Response Relationship Drug Vulvar Neoplasms business.industry Cancer medicine.disease Xenograft Model Antitumor Assays Culture Media Transplantation 030104 developmental biology Paget Disease Extramammary Cancer research Feasibility Studies Intercellular Signaling Peptides and Proteins Female Skin cancer business Chemosensitivity assay Ex vivo medicine.drug |
| Zdroj: | Journal of dermatological science. 99(3) |
| ISSN: | 1873-569X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect