INTEGRINS - A FAMILY OF CELL-ADHESION REC EPTORS

Integrins are a family of cell adhesion molecules (CAM's) that mediate the communication between the intracellular and the extracellular com partments. The growing interest in CAM's is due to the essential role they play in cell-cell and cell-matrix recognition processes. These re ceptors are formed by a non-covalently associated glycoprotein complex of two distinct polypeptide chains, called, alpha and beta. The assoc iation of different subunits results in the formation of, at least, 16 different integrins that provide cells with a great versatility in th eir 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 ce lls, leukocytes, fibroblasts and platelets. b1 integrins are essential ly involved in cell-extracellular matrix interactions and beta2 subfam ily in leukocyte-leukocyte and leukocyte-endothelial cell communicatio ns. The integrin subfamily beta3 mediates the adhesion of platelets wi th fibrinogen and other ligands. During embryonic development, integri ns in association with other CAM's, play an essential role in cell mig ration and morphogenesis. Moreover, in processes like inflammation, wo und healing and thrombosis, integrins and other CAM's mediate the inte ractions among the injured tissue and circulating cells. In two geneti c diseases like the leukocyte adhesion deficiency and the Glanzmann's thrombasthenia an impairment in leukocyte-endothelial cell interaction s and platelet aggregation is detected, due to deficiencies or abnorma lities 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, homin g and cell spreading. Integrins from beta1 and beta3 subfamilies also mediate the interaction of tumor cells with platelets, facilitating th e passage of neoplastic cells through the endothelium. Specific antibo dies to integrins or soluble forms of these receptors or their ligands could eventually be used for therapeutic purposes, modulating phenome na like inflammation, thrombosis and tumor invasion.