Cellular Adhesion and Adhesion Molecules

In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhesion molecules are summarized. Introduction Cells in vivo must form contacts with their neighbours or with an extracellular matrix (ECM) in order to form tissues or organs. The macromolecular components of ECM, which are secreted by resident cells, include proteglycans, glycoproteins and collagens, which may function as tracks, directing migrating cells along a particular route. Other members of the ECM, including adhesive molecules such as laminin, vitronectin and fibronectin, facilitate the adherence of cells to their substratum as they migrate. ECM not only fills intercellular spaces, shaping and strengthening many tissues, but also influences celluar functions such as state of differentiation and proliferation (1, 2, 4). Evidence originally obtained from studies with antisera against cell surface proteins revealed that the morphology of cells bound to the ECM could be modified and that these cells could become de-attached by such treatments, suggesting that specific receptors regulated the process (2). In the last 20 years, the nature of many of these cell adhesion receptors has been elucidated, while the use of synthetic peptides or proteolytic fragments of adhesive proteins has revealed the nature of cell-binding sites on these receptors (3, 4). Cell adhesion receptors identified to date mediate both homophilic adhesion (which involves binding of an adhesion molecule on one cell to the same adhesion molecule on a second cell) and heterophilic adhesion (in which an adhesion molecule on one cell type binds to a different type of cell adhesion molecule on a second cell). The T-cell interaction with antigen-presenting target cells in the immune system is the best known example of heterophilic adhesion (4). Many different molecules have been identified by using specific monoclonal antibodies (mAbs) and the subsequent identification of genes responsible for encoding these molecules has shown that they are structurally different from each other. These cell adhesion molecules can be divided into 4 major families: the cadherin superfamily, the selectins, the immunoglobulin superfamily and the Review Article