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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  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-5012-5897 (unconfirmed)
Tanaka, Koji
Giroux, Veronique
Muir, Amanda B.
Whelan, Kelly A.
Ohashi, Shinya  kyouindb  KAKEN_id
Naganuma, Seiji
Klein-Szanto, Andres J.
Shinden, Yoshiaki
Sasaki, Ken
Omoto, Itaru
Kita, Yoshiaki
Muto, Manabu  kyouindb  KAKEN_id
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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