Abstract
We report that vascular endothelial growth factor (VEGF), a major angiogenic factor, is also arequisite autocrine factor for breast carcinoma invasion in vitro and that the VEGF receptor Neuropilin-1 but not Flt-1 is essential for this function. VEGF regulates expression of the chemokine receptor CXCR4, and this VEGF target is needed for invasion but not for cell survival. CXCR4 mediates migration of breast carcinoma cells toward stromal-derived factor-1, and this migration is dependent on autocrine VEGF. Of interest, a CXCR4-inhibitory peptide that is currently in HIV clinical trials suppressed invasion. Our findings indicate that a VEGF autocrine pathway induces chemokine receptor expression in breast carcinoma cells, thus promoting their directed migration toward specific chemokines.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Antibodies / immunology
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Antibodies / pharmacology
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology*
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Cell Movement / physiology
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Cell Survival / physiology
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Chemokine CXCL12
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Chemokines, CXC / antagonists & inhibitors
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Chemokines, CXC / immunology
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Chemokines, CXC / physiology
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Culture Media, Conditioned
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Endothelial Growth Factors / biosynthesis
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Endothelial Growth Factors / physiology*
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Heterotrimeric GTP-Binding Proteins / physiology
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Humans
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Intercellular Signaling Peptides and Proteins / biosynthesis
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Intercellular Signaling Peptides and Proteins / physiology*
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Lymphokines / biosynthesis
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Lymphokines / physiology*
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Mice
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Neoplasm Invasiveness
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Neuropilin-1 / physiology
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Oligopeptides / pharmacology
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Receptors, CXCR4 / antagonists & inhibitors
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Receptors, CXCR4 / biosynthesis
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Receptors, CXCR4 / physiology*
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Signal Transduction / physiology
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Tumor Cells, Cultured
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Antibodies
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CXCL12 protein, human
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Chemokine CXCL12
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Chemokines, CXC
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Culture Media, Conditioned
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Cxcl12 protein, mouse
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Endothelial Growth Factors
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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N-alpha-acetyl-nona-D-arginine amide acetate
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Oligopeptides
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Receptors, CXCR4
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Neuropilin-1
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Heterotrimeric GTP-Binding Proteins