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Secreted growth factors directed from malignant cell to malignant cell, malignant cell to stromal cells, vascular cells and immune system cells or from stromal cells, vascular cells and immune system cells to malignant cells are essential for the growth and progression of malignant disease. Proangiogenic factors including members of the vascular endothelial growth factor (VEGF)-A family, placental growth factor, members of the fibroblast growth factor family, semaphorins, ephrins, angiopoietins, stromal-cell derived factor-1, EG-VEGF, Bv8, transforming growth factor-βs (TGFβs), and others act on endothelial cells, endothelial precursor cells and endothelial progenitor cells from the bone marrow to promote tumor growth. Platelet-derived growth factors act on pericytes. The VEGF-C and VEGF-D family members stimulate lymphangiogenesis. TGFβ secreted by malignant cells and stromal cells acts on the tumor stromal cells and on immune system cells to promote growth of the malignancy. Urokinase plasminogen activator and tissue plasminogen activator stimulate malignant cell and vascular cell migration as do numerous secreted matrix metalloproteinases. Secreted protein acidic and rich in cysteine (SPARC) stimulates the growth of malignant cells and influences malignant cell invasion and metastasis. In the bone, RANK ligand secretion can be stimulated by malignant disease to stimulate osteoclast-mediated bone resorption and allow metastasis growth. The interleukin family of secreted proteins mediates immune system activity. Immune system damping interleukins are involved in tumor immune evasion as are the chemokines monocyte chemoattractant protein 1 (MCP1) and RANTES. The large epidermal growth factor family stimulates the proliferation of epithelial malignant cells. Similarly, insulin-like growth factors and hepatocyte growth factor increase the growth of malignant tumors. Recently, the Wnt family of secreted growth factors has been identified as deregulated in multiple epithelial tumors. Many secreted growth factors are potential therapeutic targets for neutralizing antibodies or soluble receptor constructs. [ABSTRACT FROM AUTHOR]