Subconfluent endothelial cells form podosomes downstream of cytokine and RhoGTPase signaling.
Adhesion, migration and invasion of endothelial cells are prerequisites for the formation of blood vessels and have to be controlled on a subcellular level. We report that subconfluent human umbilical vein endothelial cells (HUVEC) are able to constitutively form podosomal adhesions that are sites of matrix metalloprotease concentration and matrix ... degradation. Importantly, incubation of serum-starved cells with VEGF or TNFalpha revealed the dependence of podosomes on cytokine signaling. Podosome formation was also stimulated by addition of monocytes to HUVEC. Microinjection/application of specific inhibitors or active/inactive mutants showed that regulatory pathways include Src kinase and RhoGTPase signaling, N-WASP activation and Arp2/3 complex-dependent actin nucleation. In sum, our data show that HUVEC displaying a migratory phenotype constitutively form f-actin-rich adhesions with podosomal characteristics downstream of cytokine signaling. We propose that HUVEC podosomes play an important role in endothelial cell migration and invasion.
Mesh Terms:
Actin-Related Protein 2, Actin-Related Protein 3, Actins, Bacterial Toxins, Blood Platelets, Cell Adhesion, Cell Communication, Cell Count, Cell Surface Extensions, Cells, Cultured, Coculture Techniques, Culture Media, Serum-Free, Cytokines, Cytoskeletal Proteins, Endothelial Cells, Escherichia coli Proteins, Extracellular Matrix, Humans, Matrix Metalloproteinases, Microinjections, Microscopy, Fluorescence, Monocytes, Monokines, Mutation, Nerve Tissue Proteins, Phosphotyrosine, Signal Transduction, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A, Wiskott-Aldrich Syndrome Protein, Neuronal, rho GTP-Binding Proteins, src-Family Kinases
Actin-Related Protein 2, Actin-Related Protein 3, Actins, Bacterial Toxins, Blood Platelets, Cell Adhesion, Cell Communication, Cell Count, Cell Surface Extensions, Cells, Cultured, Coculture Techniques, Culture Media, Serum-Free, Cytokines, Cytoskeletal Proteins, Endothelial Cells, Escherichia coli Proteins, Extracellular Matrix, Humans, Matrix Metalloproteinases, Microinjections, Microscopy, Fluorescence, Monocytes, Monokines, Mutation, Nerve Tissue Proteins, Phosphotyrosine, Signal Transduction, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A, Wiskott-Aldrich Syndrome Protein, Neuronal, rho GTP-Binding Proteins, src-Family Kinases
Exp. Cell Res.
Date: Jul. 15, 2005
PubMed ID: 15894313
View in: Pubmed Google Scholar
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