1. Stromal Cell–Derived Factor-1/Chemokine (C-X-C Motif) Ligand 12 Stimulates Human Hepatoma Cell Growth, Migration, and Invasion
- Author
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Liliane Gattegno, Marianne Ziol, Veronique Friand, Aurelie Poiré, Michel Kraemer, Severine Brulé-Donneger, Jany Vassy, Nathalie Charnaux, Pierre Nahon, Odile Sainte-Catherine, Line Saffar, Thomas Chaigneau, Jean-Loup Salzmann, Angela Sutton, Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), and Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
STELLATE CELLS ,Cancer Research ,Chemokine receptor CCR5 ,TUMOR-CELLS ,Fluorescent Antibody Technique ,CHEMOKINE RECEPTOR CXCR4 ,MEDIATED APOPTOSIS ,ACTIVATION ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,HEPATOCELLULAR-CARCINOMA ,Stromal cell-derived factor 1 ,Phosphorylation ,Glycosaminoglycans ,0303 health sciences ,Neovascularization, Pathologic ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Liver Neoplasms ,BREAST-CANCER CELLS ,Flow Cytometry ,3. Good health ,Cell biology ,Oncology ,030220 oncology & carcinogenesis ,EXTRACELLULAR SIGNAL ,RNA Interference ,Mitogen-Activated Protein Kinases ,Signal transduction ,MESSENGER-RNA ,Chemokines, CXC ,Receptors, CXCR4 ,Carcinoma, Hepatocellular ,Stromal cell ,FACTOR-I ,Focal adhesion ,03 medical and health sciences ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,Protein kinase A ,Molecular Biology ,CXCL16 ,Cell Proliferation ,030304 developmental biology ,Tyrosine phosphorylation ,Chemokine CXCL12 ,chemistry ,biology.protein ,Cancer research ,Tyrosine ,Syndecan-4 ,Syndecan-1 ,Stromal Cells ,Syndecan-2 - 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-α–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 β-d-xyloside treatment of the cells, or by c-jun NH2-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. (Mol Cancer Res 2007;5(1):21–33)
- Published
- 2007