Modulation of tumor endothelial cell marker 7 expression during endothelial cell capillary morphogenesis

Angiogenesis, the process of new blood vessel formation from preexisting capillaries, is a multistep process. The principle cell type in this process is endothelial cells which are required to undergo proliferation, migration, differentiation, and coalescence into cord-like structures with a central lumen. However, the molecular and cellular mechanisms that regulate this process require further investigation. In this study, we have used the fibrin/fibrinogen-based three-dimensional culture to enrich for primary cultured mouse aortic endothelial cells, and to induce endothelial cell capillary morphogenesis. We found among all the cell surface markers examined that only TEM7 expression was up-regulated upon endothelial cells capillary morphogenesis. In addition, inhibition of capillary morphogenesis by serum stimulation completely blocked TEM7 expression. In contrast, stimulation of endothelial cell capillary morphogenesis with PMA enhanced TEM7 expression. Furthermore, incubation of endothelial cells with a recombinant extracellular domain of TEM7 blocked capillary morphogenesis in three-dimensional cultures. These results suggest that TEM7 is a novel protein whose cell surface expression is essential during endothelial cell capillary morphogenesis.