Endothelial Monocyte Activating Polypeptide II Induces Endothelial Cell Apoptosis and May Inhibit Tumor Angiogenesis

• Published in: Microvascular research 2000-07, Vol.60 (1), p.70-80
• Main Authors: Berger, Adam C., Alexander, H.Richard, Tang, Guangquing, Wu, Peter S., Hewitt, Stephen M., Turner, Ewa, Kruger, Erwin, Figg, William D., Grove, Andrew, Kohn, Elise, Stern, David, Libutti, Steven K.
• Format: Article
• Language: English
• Subjects: 3T3 Cells - drug effects; angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Aorta - drug effects; apoptosis; Apoptosis - drug effects; Arabidopsis Proteins; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cell Division - drug effects; Chemical agents; Cycloheximide - pharmacology; Cytokines; EMAP-II; 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; Medical sciences; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Mice; Mice, Nude; necrosis; 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; Rats; Recombinant Fusion Proteins - pharmacology; RNA-Binding Proteins - biosynthesis; RNA-Binding Proteins - genetics; RNA-Binding Proteins - pharmacology; RNA-Binding Proteins - physiology; tumor; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology; Tumors; Umbilical Veins
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1006/mvre.2000.2249

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.