title: Rat hepatic stellate cells alter the gene expression profile and promote the growth, migration and invasion of hepatocellular carcinoma cells.
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.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Le-Yuan
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Liu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Qin-An
authors.initials: QA
authors.lastname: Jia
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Yin-Ying
authors.initials: YY
authors.lastname: Dong
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Yun-Hong
authors.initials: YH
authors.lastname: Xia
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Sheng-Long
authors.initials: SL
authors.lastname: Ye
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011915:Rats, Inbred BUF; D059467:Transcriptome; D014184:Transplantation, Homologous
chemical_list: D017228:Hepatocyte Growth Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
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