Molecular mechanism and regulation of angiogenesis

Persistent angiogenesis plays a crucial role in the development of solid tumors, as the growth of solid tumors and distant metastases are found to be dependent on tumor angiogenesis. Angiogenesis is regulated by the balance between angiogenic factors and angiogenesis inhibitors. When angiogenic factors prevail against angiogenesis inhibitors and stimulate endothelial cells (ECs), ECs start to degrade the extracellular matrices, migrate into the interstitial space, proliferate, and organize neovessels. Our laboratory is interested in the molecular mechanism of angiogenesis, especially transcriptional regulation of ECs during angiogenesis. We observed that the transcription factor ETS-1 was induced in ECs in response to typical angiogenic factors including VEGF and bFGF. Moreover, ETS-1 converted ECs to an invasive phenotype by inducing the expression of matrix metalloproteinase- 1 (MMP-1), MMP-3, MMP-9, and integrin β₃ as target genes. These results suggest that ETS-1 can be a molecular target for the regulation of angiogenesis.