Document Detail

Functional expression of CXC chemokine recepter-4 mediates the secretion of matrix metalloproteinases from mouse hepatocarcinoma cell lines with different lymphatic metastasis ability.
MedLine Citation:
PMID:  16973405     Owner:  NLM     Status:  MEDLINE    
CXC chemokine recepter-4 (CXCR4) and its ligand, stromal cell-derived factor-1alpha (SDF-1alpha) have been implicated in the organ-specific metastasis of several malignancies. Hca-F and its syngeneic cell line Hca-P are mouse hepatocarcinoma cell lines with high and low potential of lymphatic metastasis, respectively. Previous studies showed that the secretion of matrix metalloproteinases (MMPs) associated with the metastatic ability of Hca-F and Hca-P cell line depending on the lymph node environment. However, the mechanism of this process has remained unclear. This study investigated the roles of CXCR4 on Hca-F cell and SDF-1alpha of lymph node in lymphatic metastasis. The RT-PCR and Flow cytometry analysis results show that Hca-F cells express higher level CXCR4 mRNA and cell-surface CXCR4 protein, as compared with Hca-P cells. Treatment of recombinant SDF-1alpha proteins induced greater amount of calcium-flux in Hca-F cells than that in Hca-P cells, demonstrating higher functional CXCR4 expression on Hca-F cells than that on Hca-P cells. Furthermore, both the cell-free extratcs of lymph node and recombinant SDF-1alpha proteins induced secretions of active MMP-9 and MMP-2 from Hca-F cells in vitro. But those secretions were significantly reduced by blockade of cell surface CXCR4 with rabbit anti-mouse CXCR4 polyclonal antibody (pAb) and neutralization of SDF-1alpha in lymph node extracts with rabbit anti-mouse SDF-1alpha pAb as well. These results suggest that the CXCR4/SDF-1alpha system mediates active MMP-9 and MMP-2 secretion from Hca-F and Hca-P cells, which facilitates lymphogenous metastasis of those cells consequently.
Haiying Chu; Huimin Zhou; Yanli Liu; Xinyu Liu; Yichuan Hu; Jianing Zhang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-14
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  39     ISSN:  1357-2725     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2007  
Date Detail:
Created Date:  2006-10-18     Completed Date:  2007-02-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  197-205     Citation Subset:  IM    
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 465 Zhongshan Road, Dalian 116027, Liaoning Province, China.
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MeSH Terms
Carcinoma, Hepatocellular / genetics,  metabolism*,  pathology
Cell Line, Tumor
Chemokine CXCL12
Chemokines, CXC / metabolism,  pharmacology
Gene Expression Regulation, Neoplastic*
Lymph Nodes / metabolism,  pathology
Matrix Metalloproteinase 2 / genetics,  secretion*
Matrix Metalloproteinase 9 / genetics,  secretion*
Neoplasm Metastasis
Neoplasm Proteins / genetics,  metabolism*
Receptors, CXCR4 / biosynthesis*,  genetics
Reg. No./Substance:
0/Chemokine CXCL12; 0/Chemokines, CXC; 0/Cxcl12 protein, mouse; 0/Neoplasm Proteins; 0/Receptors, CXCR4; EC Metalloproteinase 2; EC Metalloproteinase 9

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