ARTICLE NO. EX973799 Alteration of Interendothelial Adherens Junctions Following Tumor Cell±Endothelial Cell Interaction in Vitro

mary tumor to distant sites. In order to establish new The integrity of the vascular endothelium is mainly tumor foci, circulating tumor cells must escape from dependent upon the organization of interendothelial the vascular system. The extravasation process can be adherens junctions (AJ). These junctions are formed summarized as a sequence of events which include tu-by the homotypic interaction of a transmembrane pro- mor cell adhesion to the vascular endothelium, tumor tein, vascular endothelial cadherin (VE-cadherin), cell-mediated opening of endothelial cell-to-cell junc-which is complexed to an intracellular protein net- tions, adhesion to the underlying basement membrane, work including a-, b-, and g-catenin. Additional pro- and subsequent invasion of the host tissue [1]. teins such as vinculin and a-actinin have been sug- The endothelium forms a continuous permselective gested to link the VE-cadherin/catenin complex to the barrier that regulates the passage of plasma proteins actin-based cytoskeleton. During the process of hema- and circulating cells from blood to tissue. The perme-togenous metastasis, circulating tumor cells must dis- ability of the endothelium depends upon specializedrupt these intercellular junctions in order to extrava-junctions that are responsible for the lateral plasmasate. In the present study, we have investigated the membrane cohesion between adjacent endothelial cellsin¯uence of tumor cell±endothelial cell interaction (EC). On the basis of morphological and functionalupon interendothelial AJ. We show that human breas