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ID 56123
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Eguchi, Takanori Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Sogawa, Chiharu Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Okusha, Yuka Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Uchibe, Kenta Department of Oral Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Iinuma, Ryosuke JSR Life Sciences Corporation
Ono, Kisho Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Nakano, Keisuke Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School
Murakami, Jun Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School
Itoh, Manabu JSR Life Sciences Corporation
Arai, Kazuya JSR Life Sciences Corporation
Fujiwara, Toshifumi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Namba, Yuri Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Murata, Yoshiki Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Ohyama, Kazumi Radio Isotope Research Center, Okayama University Dental School
Shimomura, Manami Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center
Okamura, Hirohiko Department of Oral Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Takigawa, Masaharu Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School
Nakatsura, Tetsuya Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center
Kozaki, Kenichi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Okamoto, Kuniaki Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Calderwood, Stuart K. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School
Abstract
Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression.
Published Date
2018-02-07
Publication Title
PlosOne
Volume
volume13
Issue
issue2
Publisher
Public Library Science
Start Page
e0191109
ISSN
19326203
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
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isVersionOf https://doi.org/10.1371/journal.pone.0191109