Rat hepatic stellate cells alter the gene expression profile and promote the growth, migration and invasion of hepatocellular carcinoma cells

Wang,Zhi-Ming; Zhou,Le-Yuan; Liu,Bin-Bin; Jia,Qin-An; Dong,Yin-Ying; Xia,Yun-Hong; Ye,Sheng-Long

doi:10.3892/mmr.2014.2435

Rat hepatic stellate cells alter the gene expression profile and promote the growth, migration and invasion of hepatocellular carcinoma cells

Authors:
- Zhi-Ming Wang
- Le-Yuan Zhou
- Bin-Bin Liu
- Qin-An Jia
- Yin-Ying Dong
- Yun-Hong Xia
- Sheng-Long Ye
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Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
Published online on: July 31, 2014 https://doi.org/10.3892/mmr.2014.2435
Pages: 1725-1733
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The aim of the present study was to examine the effects of activated hepatic stellate cells (HSCs) and their paracrine secretions, on hepatocellular cancer cell growth and gene expression in vitro and in vivo. Differentially expressed genes in McA-RH7777 hepatocellular carcinoma (HCC) cells following non-contact co-culture with activated stellate cells, were identified by a cDNA microarray. The effect of the co-injection of HCC cells and activated HSCs on tumor size in rats was also investigated. Non-contact co-culture altered the expression of 573 HCC genes by >2-fold of the control levels. Among the six selected genes, ELISA revealed increased protein levels of hepatic growth factor, matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9). Incubation of HCC cells with medium conditioned by activated HSCs significantly increased the proliferation rate (P<0.001), migration rate and the number of invasive HCC cells (P=0.001). Co-injection of HCC cells and activated HSCs into rats significantly increased the weight of the resulting HCC tumors (P<0.01). The paracrine activity of activated HSCs markedly altered the gene expression profile of HCC cells and affected their growth, migration and invasiveness. The results from the present study indicate that the interaction between the activated HSCs and HCC has an important role in the development of HCC.

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