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Title 

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

Authors 

Hong Ryul JungHyun Mi KangJea Woon RyuDae Soo KimKyung Hee NohEun Su KimHo-Joon LeeKyung-Sook ChungHyun Soo ChoNam-Soon KimDong-Soo ImJung Hwa LimCho Rok Jung

Publisher 

Nature Publishing Group

Issue Date 

2017

Citation 

Scientific Reports

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

Link 

http://dx.doi.org/10.1038/s41598-017-10828-7

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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