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Hepatic stellate cells stimulate HCC cell migration via Laminin-5 production.
MedLine Citation:
PMID:  21413933     Owner:  NLM     Status:  Publisher    
Activated Hepatic stellate cells (HSCs) are the main source of extracellular matrix proteins present in cirrhotic liver on which hepatocellular carcinoma (HCC) commonly develops. HCC cells behave differently according differences in the surrounding microenvironment. In this study we investigate a mechanism whereby HSCs modulate the migratory activity of HCC cells. We used primary cultures of human HSCs to investigate their effect on Hep3B, Alexander, HLE and HLF HCC cells. The expression of Laminin-5 (Ln-) was documented at transcript and protein levels both in vitro and in vivo. HCC cells strongly adhere, migrate and spread in the presence of HSCs conditioned media and of co-culture. HSCs produce and secrete Ln-5 in the conditioned medium. The electrophoretic pattern of secreted Ln-5 is consistent with that of a migratory substrate, showing the presence of the g2x fragment. Blocking antibodies against Ln-5 inhibit HCC migration in the presence of HSCs conditioned media. HCC cells migrate very poorly in the presence of Ln-5 immuno-depleted HSCs conditioned medium. HCC migration in the presence of HSCs is dependent on the MEK/Erk but not the PI3K/Akt pathway. HSCs conditioned medium, as well as Ln-5, activates the MEK/Erk but not the PI3K/Akt pathway. In human HCC tissues, Ln-5 is mainly distributed along a-SMA positive cells, whereas in peritumoral tissues Ln-5 is absent. HSCs stimulate HCC migration via the production and secretion of Ln-5.
Angela Santamato; Emilia Fransvea; Francesco Dituri; Alessandra Caligiuri; Michele Quaranta; Tomoaki Niimi; Massimo Pinzani; Salvatore Antonaci; Gianluigi Giannelli
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-18
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  -     ISSN:  1470-8736     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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