Document Detail


Role of the Stromal-derived factor-1 (SDF-1) - CXCR4 Axis in the Interaction Between Hepatic Stellate Cells and Cholangiocarcinoma.
MedLine Citation:
PMID:  22727731     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Cholangiocarcinoma (CCA) is highly fatal because of early invasion, widespread metastasis and lack of an effective therapy. Migration, invasion and metastasis of CCA cells are modulated by signals received from stromal cells. The SDF-1-CXCR4 axis emerges as a pivotal regulator of migration and survival of different tumor cells. AIM OF THE STUDY: Aim of the present study was to characterize the interaction between CCA cells and human hepatic stellate cells (hHSC) focusing on the role of SDF-1. MATERIALS AND METHODS: The intrahepatic CCA cell line HuCCT-1 and primary hHSC were used for this study. RNA expression was examined by RTQ-PCR and protein expression by western blotting. Immunofluorescence microscopy and immunohystochemistry were also employed. Migration of CCA cells was assessed using modified Boyden chambers. RESULTS: CXCR4 was clearly expressed by CCA cells in human CCA liver specimens. SDF-1 and hHSC conditioned medium (CM) promoted HuCCT-1 cell migration which was abrogated by pre-incubation with AMD3100, a non-peptide antagonist of the CXCR4 receptor. In addition, HuCCT-1 cells silenced for CXCR4 did not migrate in presence of SDF-1. Both P-ERK and p-AKT were implicated in HuCCT-1 migration and showed a biphasic trend under stimulation of SDF-1. Finally, SDF-1 induced apoptotic rescue of HuCCT-1 cells by binding to CXCR4. CONCLUSIONS: Our study demonstrates that CCA cells migration and survival are modulated by the cross talk between SDF-1, released by hHSC, and HuCCT-1 cells bearing the CXCR4.
Authors:
Alessandra Gentilini; Krista Rombouts; Sara Galastri; Alessandra Caligiuri; Eleonora Mingarelli; Tommaso Mello; Fabio Marra; Stefano Mantero; Massimo Roncalli; Pietro Invernizzi; Massimo Pinzani
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-19
Journal Detail:
Title:  Journal of hepatology     Volume:  -     ISSN:  0168-8278     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Department of Internal Medicine, Center for Research, High Education and Transfer DENOTHE, University of Florence, Italy, Largo Brambilla 3, 50134, Florence, Italy.
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