Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment
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 t...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/7053872 |
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| author | Tatsuya Usui Masashi Sakurai Shuhei Enjoji Hideyoshi Kawasaki Koji Umata Takashi Ohama Nobuyuki Fujiwara Ryotaro Yabe Shunya Tsuji Hideyuki Yamawaki Shoichi Hazama Hiroko Takenouchi Masao Nakajima Ryouichi Tsunedomi Nobuaki Suzuki Hiroaki Nagano Koichi Sato |
| author_facet | Tatsuya Usui Masashi Sakurai Shuhei Enjoji Hideyoshi Kawasaki Koji Umata Takashi Ohama Nobuyuki Fujiwara Ryotaro Yabe Shunya Tsuji Hideyuki Yamawaki Shoichi Hazama Hiroko Takenouchi Masao Nakajima Ryouichi Tsunedomi Nobuaki Suzuki Hiroaki Nagano Koichi Sato |
| author_sort | Tatsuya Usui |
| collection | DOAJ |
| description | 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, α-smooth muscle actin (SMA), was observed in normal organoids. Expression of E-cadherin, MUC2, vimentin, and α-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. |
| format | Article |
| id | doaj-art-fc8bb372c4704bf9b693b80671eeaa11 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-fc8bb372c4704bf9b693b80671eeaa112025-02-03T01:32:30ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/70538727053872Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor MicroenvironmentTatsuya Usui0Masashi Sakurai1Shuhei Enjoji2Hideyoshi Kawasaki3Koji Umata4Takashi Ohama5Nobuyuki Fujiwara6Ryotaro Yabe7Shunya Tsuji8Hideyuki Yamawaki9Shoichi Hazama10Hiroko Takenouchi11Masao Nakajima12Ryouichi Tsunedomi13Nobuaki Suzuki14Hiroaki Nagano15Koichi Sato16Laboratory of Veterinary Toxicology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada, Aomori 034-8628, JapanDepartment of Translational Research and Developmental Therapeutics against Cancer, School of Medicine, Yamaguchi University, 1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, JapanDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, JapanDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, JapanDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, JapanDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, JapanDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, JapanLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, JapanTumor 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, α-smooth muscle actin (SMA), was observed in normal organoids. Expression of E-cadherin, MUC2, vimentin, and α-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.http://dx.doi.org/10.1155/2016/7053872 |
| spellingShingle | Tatsuya Usui Masashi Sakurai Shuhei Enjoji Hideyoshi Kawasaki Koji Umata Takashi Ohama Nobuyuki Fujiwara Ryotaro Yabe Shunya Tsuji Hideyuki Yamawaki Shoichi Hazama Hiroko Takenouchi Masao Nakajima Ryouichi Tsunedomi Nobuaki Suzuki Hiroaki Nagano Koichi Sato Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment Stem Cells International |
| title | Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment |
| title_full | Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment |
| title_fullStr | Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment |
| title_full_unstemmed | Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment |
| title_short | Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment |
| title_sort | establishment of a novel model for anticancer drug resistance in three dimensional primary culture of tumor microenvironment |
| url | http://dx.doi.org/10.1155/2016/7053872 |
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