Heterogeneity of endothelial cells--role in vessel specialization and cooperation in vasculogenic mimicry.

Among endothelial cells (ECs), subpopulations are mainly distinguished in terms of maturation, tissue specialization and functions. Heterogeneity is an important characteristic of endothelial cells responsible for organ-specific cell and molecule delivery. Endothelial cell heterogeneity is a key to embryonic development as well as cell recruitment in adult organism during the immune response; it determines also the pathologic spreading of diseases, such as cancer invasion and infectious disease progression among species. Heterogeneity is also a feature of intra-organ specialization of endothelial cells. ECs are highly reactive to the microenvironment and their condition reflects healthy vs. diseased states. They respond to tissue hypoxia which brings a new parameter to endothelial heterogeneity. Hypoxia changes the phenotype and biology of ECs by turning on angiogenesis to restore physioxia. Highly responsive to hypoxia are the endothelial precursor cells (EPCs) and the selected cancer stem cell (CSC) populations, the most aggressive dedifferentiated tumor cells. They cooperate with one another and contribute to the vascular mimicry process of angiogenesis. This has a most effective impact on tumor cells escape and spreading.