Cell spheroids with enhanced aggressiveness to mimic human liver cancer In vitro and In vivo

Cited 37 time in scopus
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Title
Cell spheroids with enhanced aggressiveness to mimic human liver cancer In vitro and In vivo
Author(s)
Hong Ryul Jung; Hyun Mi Kang; Jea Woon Ryu; Dae Soo KimKyung Hee Noh; Eun Su Kim; Ho-Joon Lee; Kyung-Sook ChungHyun Soo ChoNam-Soon Kim; Dong-Soo Im; Jung Hwa LimCho Rok Jung
Bibliographic Citation
Scientific Reports, vol. 7, pp. 10499-10499
Publication Year
2017
Abstract
We fabricated a spheroid-forming unit (SFU) for efficient and economic production of cell spheroids. We optimized the protocol for generating large and homogenous liver cancer cell spheroids using Huh7 hepatocellular carcinoma (HCC) cells. The large Huh7 spheroids showed apoptotic and proliferative signals in the centre and at the surface, respectively. In particular, hypoxia-induced factor-1 alpha (HIF-1α) and ERK signal activation were detected in the cell spheroids. To diminish core necrosis and increase the oncogenic character, we co-cultured spheroids with 2% human umbilical vein endothelial cells (HUVECs). HUVECs promoted proliferation and gene expression of HCC-related genes and cancer stem cell markers in the Huh7 spheroidsby activating cytokine signalling, mimicking gene expression in liver cancer. HUVECs induced angiogenesis and vessel maturation in Huh7 spheroids in vivo by activating epithelial-mesenchymal transition and angiogenic pathways. The large Huh7 cell spheroids containing HUVECs survived at higher concentrations of anti-cancer drugs (doxorubicin and sorafenib) than did monolayer cells. Our large cell spheroid provides a useful in vitro HCC model to enable intuitive observation for anti-cancer drug testing
ISSN
2045-2322
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41598-017-10828-7
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Research on National Challenges > 1. Journal Articles
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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