How endothelial cell organo-specificity mediates circulating cell homing.

Normal and transformed cells home into tissues from the circulation in a very selective way thanks to highly complex molecular mechanisms that govern cell-to-cell interactions and drive the homing of circulating cells so that it is achieved properly. Because this is characterized by a resulting high selectivity, it constitutes a template for targeted drug-, gene- or cell-therapy strategies. Designing a mimetic-based therapy requires the identification of the responsible selective molecules, but also their mechanisms of action and interactions with their ligands together with their biological modulation and regulation. This homing/invasion event is decisive at the level of the endothelium that lines the vessel walls. Since cell-to-cell interactions mean a double recognition process, this review will illustrate the part played by the endothelial cells (ECs) and their adhesion molecules: the protein as well as the glycan point of view, the chronology, and the environmental modulation of EC adhesion molecule expression. These characteristics should provide keys to understanding the resulting overall specificity of cell localization. Taking into account the cytokine microenvironment, a fundamental role was recently documented for locally secreted chemokines which act through their restricted presentation by endothelial cells. As such, chemokines contribute to illustrating the concept of endothelial organo-specificity which is approached here, uncovering the role of glycoconjugate signaling as the hallmark of refined cellular recognition, and discussed in the context of potential drug design against site-directed diseases such as metastases, inflammatory leukocyte recruitment, and tumor/inflammation-induced angiogenesis.