Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells

Takashi Kijima(University of Pennsylvania), Hiroshi Nakagawa(University of Pennsylvania), Masataka Shimonosono(Kagoshima University), Prasanna M. Chandramouleeswaran(University of Pennsylvania), Takeo Hara(Osaka University), Varun Sahu(University of Pennsylvania), Yuta Kasagi(Children's Hospital of Philadelphia), Osamu Kikuchi(Kyoto University), Koji Tanaka(Osaka University), Véronique Giroux(University of Pennsylvania), Amanda B. Muir(Children's Hospital of Philadelphia), Kelly A. Whelan(University of Pennsylvania), Shinya Ohashi(Kyoto University), Seiji Naganuma(Kōchi University), Andres J. Klein–Szanto(Fox Chase Cancer Center), Yoshiaki Shinden(Kagoshima University), Ken Sasaki(Kagoshima University), Itaru Omoto(Kagoshima University), Yoshiaki Kita(Kagoshima University), Manabu Muto(Kyoto University), Adam J. Bass(Harvard University), J. Alan Diehl(Medical University of South Carolina), Gregory G. Ginsberg(University of Pennsylvania), Yuichiro� Doki(Osaka University), Masaki Mori(Osaka University), Yasuto Uchikado(Kagoshima University), Takaaki Arigami(Kagoshima University), Narayan G. Avadhani(University of Pennsylvania), Devraj Basu(University of Pennsylvania), Anil K. Rustgi(University of Pennsylvania), Shoji Natsugoe(Kagoshima University)
Cellular and Molecular Gastroenterology and Hepatology
September 14, 2018
10.1016/j.jcmgh.2018.09.003
Cited by 155Open Access
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Abstract

Background & Aims: . We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. Methods: . Results: = 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.

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