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.