Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4.
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.
Bachelder
Robin E
RE
Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. rbacheld@caregroup.harvard.edu
Wendt
Melissa A
MA
Mercurio
Arthur M
AM
D016475:3T3 Cells; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D009361:Neoplasm Invasiveness; D039942:Neuropilin-1 / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; C515256:Cxcl12 protein, mouse; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C094365:N-alpha-acetyl-nona-D-arginine amide acetate; D009842:Oligopeptides; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1; D020962:Heterotrimeric GTP-Binding Proteins