Abstract
Endothelial monocyte activating polypeptide II (EMAP-II) is a tumor-derived cytokine with potent effects on endothelial cells in vitro and in vivo including upregulation of tissue factor and the sensitization of human melanoma to systemic TNF treatment via its effects on the tumor vasculature. We investigated the effects of EMAP-II on tumor growth, angiogenesis, vasculogenesis, and apoptosis. EMAP-II inhibited endothelial cell proliferation, vasculogenesis, and neovessel formation. In vivo growth of human melanoma lines expressing high amounts of EMAP-II demonstrated slower growth, smaller tumors, and increased amounts of tumor necrosis than those expressing lower amounts of EMAP-II. EMAP-II induced endothelial-cell-specific apoptosis via a pathway that includes upregulation of the Fas-associated death domain and downregulation of Bcl-2. EMAP-II appears to have important effects on angiogenesis and may play a role in regulating tumor vascular growth.
MeSH terms
-
3T3 Cells / drug effects
-
Angiogenesis Inhibitors / pharmacology*
-
Animals
-
Aorta / drug effects
-
Apoptosis / drug effects*
-
Arabidopsis Proteins*
-
Cell Division / drug effects
-
Cycloheximide / pharmacology
-
Cytokines*
-
Endothelium, Vascular / cytology
-
Endothelium, Vascular / drug effects*
-
Fatty Acid Desaturases / biosynthesis
-
Fatty Acid Desaturases / genetics
-
Female
-
Gene Expression Regulation, Neoplastic / drug effects
-
Genes, bcl-2
-
Humans
-
Lipopolysaccharides / pharmacology
-
Lung / blood supply
-
Melanoma / genetics
-
Melanoma / metabolism
-
Melanoma / pathology
-
Mice
-
Mice, Nude
-
Neoplasm Proteins / biosynthesis
-
Neoplasm Proteins / genetics
-
Neoplasm Proteins / pharmacology
-
Neoplasm Proteins / physiology*
-
Neoplasm Transplantation
-
Neovascularization, Pathologic / drug therapy*
-
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
-
RNA-Binding Proteins / biosynthesis
-
RNA-Binding Proteins / genetics
-
RNA-Binding Proteins / pharmacology
-
RNA-Binding Proteins / physiology*
-
Rats
-
Recombinant Fusion Proteins / pharmacology
-
Tumor Cells, Cultured
-
Tumor Necrosis Factor-alpha / pharmacology
-
Umbilical Veins
Substances
-
Angiogenesis Inhibitors
-
Arabidopsis Proteins
-
Cytokines
-
Lipopolysaccharides
-
Neoplasm Proteins
-
Proto-Oncogene Proteins c-bcl-2
-
RNA-Binding Proteins
-
Recombinant Fusion Proteins
-
Tumor Necrosis Factor-alpha
-
small inducible cytokine subfamily E, member 1
-
Cycloheximide
-
Fatty Acid Desaturases
-
Fad7 protein, Arabidopsis