Document Detail

Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma.
MedLine Citation:
PMID:  19175606     Owner:  NLM     Status:  MEDLINE    
Liver cirrhosis is the main risk factor for the development of hepatocellular carcinoma (HCC). Activated hepatic stellate cells (HSC) are the effector cells of hepatic fibrosis and also infiltrate the HCC stroma where they might play a critical role in HCC progression. Here we aimed to analyze the effects of activated HSC on the proliferation and growth of HCC cell lines in vitro and in vivo. Conditioned media (CM) collected from HSC significantly induced proliferation and migration of HCC cells cultured in monolayers. In a 3-dimensional spheroid coculture system, HSC promoted HCC growth and diminished the extent of central necrosis. In accordance, in vivo simultaneous implantation of HSC and HCC cells into nude mice promoted tumor growth and invasiveness, and inhibited necrosis formation. As potential mechanism of the tumorigenic effects of HSC we identified activation of NFkappaB and extracellular-regulated kinase (ERK) in HCC cells, two signaling cascades that play a crucial role in HCC progression. In summary, our data indicate that stromal HSC promotes HCC progression and suggest the HSC-HCC interaction as an interesting tumor differentiation-independent target for therapy of this highly aggressive cancer.
Thomas Amann; Frauke Bataille; Thilo Spruss; Marcus Mühlbauer; Erwin Gäbele; Jürgen Schölmerich; Paul Kiefer; Anja-Katrin Bosserhoff; Claus Hellerbrand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-21
Journal Detail:
Title:  Cancer science     Volume:  100     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-20     Completed Date:  2009-06-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  646-53     Citation Subset:  IM    
Department of Internal Medicine I, University of Regensburg, D-93053, Regensburg, Germany.
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MeSH Terms
Carcinoma, Hepatocellular / pathology*
Cell Line, Tumor
Cell Movement / drug effects*
Cell Proliferation / drug effects*
Coculture Techniques
Culture Media, Conditioned / pharmacology*
Enzyme Activation
Hepatic Stellate Cells / metabolism*
Liver Neoplasms / pathology*
Mice, Nude
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
NF-kappa B / metabolism
Neurotrophin 3 / genetics,  metabolism
Organ Culture Techniques
RNA, Messenger / analysis
Xenograft Model Antitumor Assays
Reg. No./Substance:
0/Culture Media, Conditioned; 0/NF-kappa B; 0/Neurotrophin 3; 0/RNA, Messenger; EC Protein Kinase 1; EC Protein Kinase 3

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