Roles of molecules involved in epithelial/mesenchymal transition during angiogenesis.

Formation of vessels requires "epithelial-mesenchymal" transition of endothelial cells, with several modifications at the level of endothelial cell plasma membranes. These processes are associated with redistribution of cell-cell and cell-substrate adhesion molecules, cross talk between external ECM and internal cytoskeleton through focal adhesion molecules and the expression of several proteolytic enzymes, including matrix metalloproteases and serine proteases. These enzymes with their degradative action on ECM components, generate molecules acting as activators and/or inhibitors of angiogenesis. The purpose of this review is to provide an overview of the molecules involved in epithelial-mesenchymal transaction, including: the ECM, the cadherins, the integrins, the focal adhesion molecules, and the proteolytic enzymes. The initial clinical trials using physiological, synthetic and immunologic inhibitors against the described molecules for cancer treatment did not show the expected efficacy, in terms of reducing tumor progression. This is due to the fact that these molecules have multiple roles both in angiogenesis and tumor progression. Therefore, developing a strategy against induced angiogenesis requires an overview of all actors which are involved in this phenomenon.