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Stem Cells International - Volume 2016 2016, Article ID 7053872, 10 pages -

Research Article

Laboratory of Veterinary Toxicology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan

Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan

Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan

Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada, Aomori 034-8628, Japan

Department of Translational Research and Developmental Therapeutics against Cancer, School of Medicine, Yamaguchi University, 1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan

Department of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan

Received 16 October 2016; Revised 28 November 2016; Accepted 6 December 2016

Academic Editor: Dominik Wolf

Copyright © 2016 Tatsuya Usui et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Tumor microenvironment has been implicated in tumor development and progression. As a three-dimensional tumor microenvironment model, air liquid interface ALI organoid culture from oncogene transgenic mouse gastrointestinal tissues was recently produced. However, ALI organoid culture system from tissues of colorectal cancer patients has not been established. Here, we developed an ALI organoid model from normal and tumor colorectal tissues of human patients. Both organoids were successfully generated and showed cystic structures containing an epithelial layer and surrounding mesenchymal stromal cells. Structures of tumor organoids closely resembled primary tumor epithelium. Expression of an epithelial cell marker, E-cadherin, a goblet cell marker, MUC2, and a fibroblast marker, vimentin, but not a myofibroblast marker -smooth muscle actin SMA, was observed in normal organoids. Expression of E-cadherin, MUC2, vimentin, and -SMA was observed in tumor organoids. Expression of a cancer stem cell marker, LGR5 in tumor organoids, was higher than that in primary tumor tissues. Tumor organoids were more resistant to toxicity of 5-fluorouracil and Irinotecan than colorectal cancer cell lines, SW480, SW620, and HCT116. These findings indicate that ALI organoid culture from colorectal cancer patients may become a novel model that is useful for examining resistance to chemotherapy in tumor microenvironment.





Author: Tatsuya Usui, Masashi Sakurai, Shuhei Enjoji, Hideyoshi Kawasaki, Koji Umata, Takashi Ohama, Nobuyuki Fujiwara, Ryotaro Yab

Source: https://www.hindawi.com/



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