FUNCTIONS, STRUCTURE, AND REGULATION OF RECEPTORS FOR CELL ADHESION PROTEINS

关键细胞外蛋白的受体，如纤维连接蛋白，胶原蛋白和

Receptors for key extracellular proteins such as fibronectin, collagen, and laminin are thought to mediate adherence, migration, and invasion by normal or tumor cells. The functions and distributions of integrin receptors for these molecules were explored using several subunit-specific monoclonal antibodies. The alpha5beta1 fibronectin receptor was found to play central roles in cell adhesion, extracellular matrix assembly, and actin cytoskeletal organization. It was found to synergize with the T-cell receptor in lymphocyte proliferation. Other members of the beta1 integrin family were found to be involved in cell-cell as well as cell-matrix interactions, e.g., in the maintenance of cell contacts and adjacent cytoskeletal organization in keratinocytes. Inhibition of beta1 integrin function disrupted fibronectin matrix assembly in several systems, and blocked normal gastrulation in embryonic development. Biosynthesis and localization of integrin receptors was found to differ in certain tumor cells. For example, the rate of maturation of beta1 subunits was accelerated in transformed human cells, and localization was disrupted in these cells and in squamous cell carcinomas. Another integrin receptor termed alpha4beta1, which binds to a cell-type specific sequence in fibronectin, was isolated from metastatic human melanoma cells. The distribution of integrin receptors reflects, and may also affect, their function: when localized to adhesion plaques, they appear to be part of an extracellular matrix assembly system and to help to retard cell migration. In rapidly migrating embryonic cells or certain tumor cells, they can be diffusely organized and more directly involved in cell migration. Further analyses of the regulation and function of these integrin receptors for extracellular proteins will provide further insights into the mechanisms of cell adhesion, migration, and invasion, and should provide novel approaches to inhibiting them more specifically.