Endothelial monocyte activating polypeptide II induces endothelial cell apoptosis and may inhibit tumor angiogenesis

Endothelial monocyte activating polypeptide II (EMAP-II) is a tumor-derived cytokine with potent effects on endothelial cells in vitro and in vivo inc luding upregulation of tissue factor and the sensitization of human melanom a to systemic TNF treatment via its effects on the tumor vasculature. We in vestigated the effects of EMAP-II on tumor growth, angiogenesis, vasculogen esis, and apoptosis. EMAP-II inhibited endothelial cell proliferation, vasc ulogenesis, and neovessel formation. In vivo growth of human melanoma lines expressing high amounts of EMAP-II demonstrated slower growth, smaller tum ors, and increased amounts of tumor necrosis than those expressing lower am ounts 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 angio genesis and may play a role in regulating tumor vascular growth.