Tumorangiogenesis: a network of cytokines.

During angiogenesis new blood vessels sprout from an existing vascular bed. This is a prerequisite for tumor growth beyond a certain size and for metastasis formation. Tumors produce a number of cytokines. The development of in vivo bio-assays for angiogenesis and in vitro analysis of endothelial cells permits characterization of these different cytokines concerning their role in angiogenesis. Some cytokines act mitogenically on endothelial cells, others have chemotactic activity or induce tube formation and some have multiple functions. A few factors are chemotactic for macrophages, infiltrating the tumor and secreting further angiogenic cytokines. Another important role in the process of angiogenesis is played by the extracellular matrix. Proteases secreted by all cell types involved (tumor cell, endothelial cell, macrophages) degrade the extracellular matrix, thereby releasing and activating angiogenic factors sequestered in the extracellular matrix. Thus tumor cells, macrophages and extracellular matrix release cytokines which together act on endothelial cells, resulting in the growth and infiltration of new blood vessels into the tumor.