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Title: A novel three-dimensional culture system maintaining the physiological extracellular matrix of fibrotic model livers accelerates progression of hepatocellular carcinoma cells
Authors: Miyauchi, Yuya
Yasuchika, Kentaro
Fukumitsu, Ken  kyouindb  KAKEN_id
Ishii, Takamichi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-7461-9653 (unconfirmed)
Ogiso, Satoshi
Minami, Takahito
Kojima, Hidenobu
Yamaoka, Ryoya
Katayama, Hokahiro
Kawai, Takayuki
Yoshitoshi-Uebayashi, Elena Yukie
Kita, Sadahiko
Yasuda, Katsutaro
Sasaki, Naoya
Uemoto, Shinji
Author's alias: 宮内, 雄也
安近, 健太郎
福光, 剣
石井, 隆道
小木曽, 聡
小島, 秀信
山岡, 竜也
片山, 外大
河合, 隆之
吉利, エレーナ幸江
喜多, 貞彦
安田, 勝太郎
佐々木, 直也
上本, 伸二
Keywords: Cancer microenvironment
Hepatocellular carcinoma
Liver fibrosis
Tissues
Issue Date: 29-Aug-2017
Publisher: Springer Nature
Journal title: Scientific Reports
Volume: 7
Thesis number: 9827
Abstract: Liver fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM) and is a strong predictor of hepatocellular carcinoma (HCC) development and progression. However, the effect of ECM in fibrotic livers on HCC cells is poorly understood. The aims of this study were to create a new culture system that retained the natural ECM of fibrotic model livers and to establish whether natural ECM regulated the characteristics of HCC cells. Using an organ decellularization technique, we created a new culture system that preserved the tissue-specific ECM of fibrotic model livers from CCl4-treated rats. The content of ECM in fibrotic model liver scaffolds was increased and the ECM microstructure was distorted. Quantitative polymerase chain reaction and immunofluorescence assays of HCC cells cultured in fibrotic model liver scaffolds for 7 days showed an epithelial-mesenchymal transition phenotype. Moreover, the ECM of fibrotic model livers promoted proliferation and chemoresistance of HCC cells. These results showed a novel effect of natural ECM in fibrotic model livers on the malignant behaviour of HCC cells. This new culture system will be useful for both understanding the cell biology of fibrotic livers and developing novel anti-cancer drugs.
Rights: © The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
URI: http://hdl.handle.net/2433/227895
DOI(Published Version): 10.1038/s41598-017-09391-y
Appears in Collections:Journal Articles

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