| Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma. | |
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MedLine Citation:
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PMID: 19175606 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-21 |
Journal Detail:
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Title: Cancer science Volume: 100 ISSN: 1349-7006 ISO Abbreviation: Cancer Sci. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-05-20 Completed Date: 2009-06-19 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: England |
Other Details:
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Languages: eng Pagination: 646-53 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine I, University of Regensburg, D-93053, Regensburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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* Humans Liver Neoplasms / pathology* Mice 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 |
| Chemical | |
Reg. No./Substance:
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0/Culture Media, Conditioned; 0/NF-kappa B; 0/Neurotrophin 3; 0/RNA, Messenger; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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