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Title: Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells
Authors: Kijima, Takashi
Nakagawa, Hiroshi
Shimonosono, Masataka
Chandramouleeswaran, Prasanna M.
Hara, Takeo
Sahu, Varun
Kasagi, Yuta
Kikuchi, Osamu
Tanaka, Koji
Giroux, Veronique
Muir, Amanda B.
Whelan, Kelly A.
Ohashi, Shinya
Naganuma, Seiji
Klein-Szanto, Andres J.
Shinden, Yoshiaki
Sasaki, Ken
Omoto, Itaru
Kita, Yoshiaki
Muto, Manabu
Bass, Adam J.
Diehl, J. Alan
Ginsberg, Gregory G.
Doki, Yuichiro
Mori, Masaki
Uchikado, Yasuto
Arigami, Takaaki
Avadhani, Narayan G.
Basu, Devraj
Rustgi, Anil K.
Natsugoe, Shoji
Author's alias: 貴島, 孝
下之薗, 将貴
原, 豪男
菊池, 理
田中, 晃司
大橋, 真也
長沼, 誠二
新田, 吉陽
佐々木, 健
尾本, 至
喜多, 芳昭
武藤, 学
土岐, 祐一郎
森, 正樹
内門, 泰斗
有上, 貴明
夏越, 祥次
Keywords: 3D Organoids
Autophagy
CD44
5-Fluorouracil
Issue Date: 2019
Publisher: Elsevier BV
Journal title: Cellular and Molecular Gastroenterology and Hepatology
Volume: 7
Issue: 1
Start page: 73
End page: 91
Abstract: Background & Aims: Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. Methods: We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naïve patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil ex vivo. Results: Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment. Conclusions: The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.
Rights: © 2019 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/2433/246431
DOI(Published Version): 10.1016/j.jcmgh.2018.09.003
PubMed ID: 30510992
Appears in Collections:Journal Articles

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