Evaluation of anticancer agents using patient-derived tumor organoids characteristically similar to source tissues

Tamura,Hirosumi; Higa,Arisa; Hoshi,Hirotaka; Hiyama,Gen; Takahashi,Nobuhiko; Ryufuku,Masae; Morisawa,Gaku; Yanagisawa,Yuka; Ito,Emi; Imai,Jun-Ichi; Dobashi,Yuu; Katahira,Kiyoaki; Soeda,Shu; Watanabe,Takafumi; Fujimori,Keiya; Watanabe,Shinya; Takagi,Motoki

doi:10.3892/or.2018.6501

Evaluation of anticancer agents using patient-derived tumor organoids characteristically similar to source tissues

Authors:
- Hirosumi Tamura
- Arisa Higa
- Hirotaka Hoshi
- Gen Hiyama
- Nobuhiko Takahashi
- Masae Ryufuku
- Gaku Morisawa
- Yuka Yanagisawa
- Emi Ito
- Jun-Ichi Imai
- Yuu Dobashi
- Kiyoaki Katahira
- Shu Soeda
- Takafumi Watanabe
- Keiya Fujimori
- Shinya Watanabe
- Motoki Takagi
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Affiliations: Medical-Industrial Translational Research Center, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan, Department of Obstetrics and Gynecology, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan
Published online on: June 18, 2018 https://doi.org/10.3892/or.2018.6501
Pages: 635-646
Copyright: © Tamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Patient-derived tumor xenograft models represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture; however, their use is low-throughput and costly. To overcome this limitation, patient-derived tumor organoids (PDOs) were established from human lung, ovarian and uterine tumor tissues, among others, to accurately and efficiently recapitulate the tissue architecture and function. PDOs were able to be cultured for >6 months, and formed cell clusters with similar morphologies to their source tumors. Comparative histological and comprehensive gene expression analyses proved that the characteristics of PDOs were similar to those of their source tumors, even following long-term expansion in culture. At present, 53 PDOs have been established by the Fukushima Translational Research Project, and were designated as Fukushima PDOs (F‑PDOs). In addition, the in vivo tumorigenesis of certain F‑PDOs was confirmed using a xenograft model. The present study represents a detailed analysis of three F‑PDOs (termed REME9, 11 and 16) established from endometrial cancer tissues. These were used for cell growth inhibition experiments using anticancer agents. A suitable high-throughput assay system, with 96- or 384‑well plates, was designed for each F‑PDO, and the efficacy of the anticancer agents was subsequently evaluated. REME9 and 11 exhibited distinct responses and increased resistance to the drugs, as compared with conventional cancer cell lines (AN3 CA and RL95-2). REME9 and 11, which were established from tumors that originated in patients who did not respond to paclitaxel and carboplatin (the standard chemotherapy for endometrial cancer), exhibited high resistance (half-maximal inhibitory concentration >10 µM) to the two agents. Therefore, assay systems using F‑PDOs may be utilized to evaluate anticancer agents using conditions that better reflect clinical conditions, compared with conventional methods using cancer cell lines, and to discover markers that identify the pharmacological effects of anticancer agents.

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