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Stromal cell-derived factor-1/chemokine (C-X-C motif) ligand 12 stimulates human hepatoma cell growth, migration, and invasion.
- Source :
-
Molecular cancer research : MCR [Mol Cancer Res] 2007 Jan; Vol. 5 (1), pp. 21-33. - Publication Year :
- 2007
-
Abstract
- In addition to their physiologic effects in inflammation and angiogenesis, chemokines are involved in cancer pathology. The aim of this study was to determine whether the chemokine stromal cell-derived factor 1 (SDF-1) induces the growth, migration, and invasion of human hepatoma cells. We show that SDF-1 G protein-coupled receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), and SDF-1 mRNA are expressed in human hepatoma Huh7 cells, which secrete and bind SDF-1. This binding depends on CXCR4 and glycosaminoglycans. SDF-1 associates with CXCR4, and syndecan-4 (SDC-4), a heparan sulfate proteoglycan at the plasma membrane of Huh7 cells, induces the growth of Huh7 cells by promoting their entry into the cell cycle, and inhibits the tumor necrosis factor-alpha-mediated apoptosis of the cells. SDF-1 also reorganizes Huh7 cytoskeleton and induces tyrosine phosphorylation of focal adhesion kinase. Finally, SDF-1 activates matrix metalloproteinase-9, resulting in increased migration and invasion of Huh7 cells. These biological effects of SDF-1 were strongly inhibited by the CXCR4 antagonist AMD3100, by a glycosaminoglycan, heparin, as well as by beta-D-xyloside treatment of the cells, or by c-jun NH(2)-terminal kinase/stress-activated protein kinase inhibitor. Therefore, the CXCR4, glycosaminoglycans, and the mitogen-activated protein kinase signaling pathways are involved in these events. The fact that reducing SDC-4 expression by RNA interference decreased SDF-1-induced Huh7 hepatoma cell migration and invasion strongly indicates that SDC-4 may be an auxiliary receptor for SDF-1. Finally, the fact that CXCR4 is expressed in hepatocellular carcinoma cells from liver biopsies indicates that the in vitro results reported here could be extended to in vivo conditions.
- Subjects :
- Carcinoma, Hepatocellular metabolism
Chemokine CXCL12
Flow Cytometry
Fluorescent Antibody Technique
Glycosaminoglycans pharmacology
Humans
Liver Neoplasms metabolism
Mitogen-Activated Protein Kinases metabolism
Neoplasm Invasiveness
Neovascularization, Pathologic
Phosphorylation
RNA Interference
RNA, Messenger antagonists & inhibitors
RNA, Messenger genetics
RNA, Messenger metabolism
Receptors, CXCR4 metabolism
Reverse Transcriptase Polymerase Chain Reaction
Stromal Cells metabolism
Stromal Cells pathology
Syndecan-1 metabolism
Syndecan-2 metabolism
Syndecan-4 antagonists & inhibitors
Syndecan-4 genetics
Syndecan-4 metabolism
Tyrosine metabolism
Carcinoma, Hepatocellular pathology
Cell Movement
Cell Proliferation
Chemokines, CXC physiology
Liver Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1541-7786
- Volume :
- 5
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cancer research : MCR
- Publication Type :
- Academic Journal
- Accession number :
- 17259344
- Full Text :
- https://doi.org/10.1158/1541-7786.MCR-06-0103