Cloning of JAM-2 and JAM-3: an Emerging Junctional Adhesion Molecular Family

Abstract

Throughout embryonic and early postnatal development, endothelial cells proliferate and differentiate to form new blood vessels via vasculogenesis and angiogenesis (1, 2). In adult organisms the endothelium defines the blood-tissue barrier and consists of non-cycling quiescent cells. These polarized cells are linked to each other by tight junctions and adherens junctions to form a continuous layer of cells. JAM (hereafter referred as JAM-1) and VE-cadherin were characterized as endothelial adhesion molecules participating in tight and adherens intercellular junctions respectively (3, 4). These molecules were shown to regulate vascular functions such as monocyte transmigration or paracellular permeability, probably as a consequence of their structural contribution to the vessel wall. It is well established that the regulated and coordinated expression of adhesion molecules is necessary to maintain normal vascular functions such as tissue homeostasis, vascular permeability, leukocyte emigration, fibrinolysis, coagulation and vasotonus. Temporary changes in the adhesion properties of vascular endothelium have been observed during inflammation, tumor growth, wounding or angiogenesis (5-7). The presence of a growing tumor increases the local concentration of angiogenic factors leading to a switch from non-cycling quiescent endothelial cells to proliferating endothelium. As a result, endothelial cells of existing vessels degrade the extracellular matrix (ECM) and invade the surrounding tissue, which leads to vascularization of tumors. During the angiogenic switch, the pattern of endothelial gene expression is modified, and the level of transcripts encoding protein s involved in cell migration or cell division is affected. For example, the balance between proteases/antiproteases such as PA/PAI1 is changed, leading to increased endothelial cell motility (8). Moreover, the treatment of endothelial cells with angiogenic factors results in a fourfold increase in α_Vβ₃ integrin expression, an adhesion molecule implicated in cell migration (9). In addition, angiogenesis was shown to modify the endothelial inflammatory response leading to abnormal expression of inflammatory adhesion molecules (10, 11). These examples do not constitute an exhaustive list, but support the hypothesis that during the angiogenic switch, the global adhesion behavior of endothelial cells is changed.