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Gene expression profiles during activation of cultured rat hepatic stellate cells by tumoral hepatocytes and fetal bovine serum

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Hepatic stellate cells (HSCs) transdifferentiate to become extracellular matrix-producing myofibroblasts during liver injury. Myofibroblasts can also promote invasion and metastasis of hepatocellular carcinoma (HCC). In this study, we determined gene expression changes in two different models of HSC activation, induction-activated HSCs (iHSCs) and culture-activated HSCs (cHSCs).

Methods

Hepatic stellate cells were isolated by density centrifugation and exposed to conditioned medium (CM) from the rat HCC cell line C5F, and fetal bovine serum (FBS). Expression of 27,100 genes in quiescent HSCs, cHSCs and iHSCs was analyzed by microarray and was confirmed on a subset of genes by real-time RT-PCR and Western blot.

Results

One thousand nine hundred sixty-seven genes were differentially expressed in cHSCs and iHSCs, including genes that encode proinflammatory factors, adhesion molecules, cell surface receptors, signaling transduction and immune factors such as Il1a, Vcam1, Ccl6, Ilr7, PRAP, osteopontin, Gp39, Raf1, Rac2, Adam17, Wnt6, MMP-9, and Cfd. C5F-CM-induced activation only partially reproduced the gene expression changes observed during FBS culture activation. iHSCs showed specific gene expression, suggesting that HCC cells can specifically induce HSC activation.

Conclusions

Induction-activated HSCs’ gene expression patterns were partially similar to and different from that of cHSCs. iHSCs might play an important role in invasion and metastasis of HCC. This study provided theoretical foundations for investigating the biology of HSCs in HCC.

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Abbreviations

HSCs:

Hepatic stellate cells

ECM:

Extracellular matrix

α-SMA:

α-Smooth muscle actin

FBS:

Fetal bovine serum

qHSCs:

Quiescent HSCs

cHSCs:

Culture-activated HSCs

iHSCs:

Induction-activated HSCs

HCC:

Hepatocellular carcinoma

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Acknowledgments

We thank Boao Biochip Co Ltd, Beijing, China, for help in cDNA microarray construction.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China

    Yunhong Xia, Rongxin Chen, Shenglong Ye, Ruixia Sun, Qiong Xue & Zhe Zhang

  2. Medical Department of Digestion, Zhongshan Hospital, Fudan University, 200032, Shanghai, China

    Zhenji Song

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  1. Yunhong Xia
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  2. Rongxin Chen
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  3. Zhenji Song
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  4. Shenglong Ye
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  5. Ruixia Sun
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  6. Qiong Xue
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  7. Zhe Zhang
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Corresponding author

Correspondence to Shenglong Ye.

Additional information

Y. Xia and R. Chen contributed equally to this study.

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Xia, Y., Chen, R., Song, Z. et al. Gene expression profiles during activation of cultured rat hepatic stellate cells by tumoral hepatocytes and fetal bovine serum. J Cancer Res Clin Oncol 136, 309–321 (2010). https://doi.org/10.1007/s00432-009-0666-5

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  • DOI: https://doi.org/10.1007/s00432-009-0666-5

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