INTEGRINS - A FAMILY OF CELL-ADHESION RECEPTORS

Integrins are a family of cell adhesion molecules (CAM's) that mediate the communication between the intracellular and the extracellular compartments. The growing interest in CAM's is due to the essential role they play in cell-cell and cell-matrix recognition processes. These receptors are formed by a non-covalently associated glycoprotein complex of two distinct polypeptide chains, called, alpha and beta. The association of different subunits results in the formation of, at least, 16 different integrins that provide cells with a great versatility in their adhesion properties. An integrin molecule comprises a cytoplasmic domain that interacts with the cytoskeleton, a transmembranous domain and an extracellular domain that binds to one or more ligands. beta1, beta2 and beta3, are the best characterized integrin subfamilies; they are expressed, in different amounts, in epithelial and endothelial cells, leukocytes, fibroblasts and platelets. b1 integrins are essentially involved in cell-extracellular matrix interactions and beta2 subfamily in leukocyte-leukocyte and leukocyte-endothelial cell communications. The integrin subfamily beta3 mediates the adhesion of platelets with fibrinogen and other ligands. During embryonic development, integrins in association with other CAM's, play an essential role in cell migration and morphogenesis. Moreover, in processes like inflammation, wound healing and thrombosis, integrins and other CAM's mediate the interactions among the injured tissue and circulating cells. In two genetic diseases like the leukocyte adhesion deficiency and the Glanzmann's thrombasthenia an impairment in leukocyte-endothelial cell interactions and platelet aggregation is detected, due to deficiencies or abnormalities in beta2 or beta3 integrin subfamilies, respectively. In tumor invasion and metastasis integrins are involved in processes like cell detachment from extracellular matrix components, cell migration, homing and cell spreading. Integrins from beta1 and beta3 subfamilies also mediate the interaction of tumor cells with platelets, facilitating the passage of neoplastic cells through the endothelium. Specific antibodies to integrins or soluble forms of these receptors or their ligands could eventually be used for therapeutic purposes, modulating phenomena like inflammation, thrombosis and tumor invasion.