ABSTRACT
Angiogenesis plays a fundamental role in development of circulation system, reorganization of reproductive system, wound healing. Pathological angiogenesis is deeply involved in a variety of diseases, particularly solid tumor growth and metastasis. However, it is not easy to study the mechanism of angiogenesis because endothelial cells proceed complex differentiation by interaction with extracellular matrix proteins and growth factors. However, human umbilical vein endothelial cells (HUVEC) form polygonal networks of capillary-like tubes in 3D Matrigel cultures. Differentiation of endothelial cells will be observed accurately by application of videomicroscopy. Thrombospondin-1 is secreted by a wide variety of cells including endothelial cells and is incorporated into their matrix. Thrombospondin-1 can modulate differentiation of endothelial cells by increasing cell-cell interactions as well as cell-substrate interactions. The current study was undertaken to determine which mechanism is involved in inhibition of angiogenesis by Thrombospondin-1. They was secreted from HUVEC during the process of angiogenesis in 3D Matrigel culture. When applied to endothelial cells attachment to the surface of Matrigel was not decreased, but spreading was decreased. In addition, bigger clusters was formed by enhancement of cell to cell binding by Thrombospondin-1. They inhibit cord and tube formation of HUVEC by inhibition of migration. These results suggest that Thrombospondin-1 inhibits angiogenesis by blocking differentiation of endothelial cells to motile phenotype in 3D Matrigel culture.