E-cadherin is a ligand for integrin α2β1

E-cadherin is a 120-kDa transmembrane glycoprotein expressed mainly on the surface of epithelial cells. The best characterised function of E-cadherin is homotypic, calcium-dependent cell-cell adhesion; however, the observation that E-cadherin is also capable of interacting with the αEβ7 integrin to mediate leukocyte cell-cell adhesion [Nature 372 (1994) 190] suggests that it also participates in heterotypic interactions. To investigate the possibility that E-cadherin may interact with integrins expressed on non-leukocytic cells, cell adhesion and solid-phase receptor-ligand binding experiments were performed using a pentameric E-cadherin construct designed to detect low affinity, high avidity interactions. HT1080 human fibrosarcoma cells specifically adhered to pentameric E-cadherin, and this adhesion was inhibited by anti-functional monoclonal antibodies directed against the integrin α2 and β1 subunits, but not by a series of antibodies recognising other subunits. This suggested that the E-cadherin receptor was α2β1, a previously characterised collagen/laminin receptor. Pentameric E-cadherin, but not monomeric E-cadherin, specifically bound, in a divalent cation-dependent manner, to both purified α2β1 and to a recombinant form of the A-domain of the α2 subunit, which has been shown to be a major ligand-binding site within this and other integrins. These findings demonstrate that E-cadherin can interact with α2β1 and suggest that heterotypic interactions between E-cadherin and integrins may be more common than originally thought. © 2002 Elsevier Science B.V. and International Society of Matrix Biology. All rights reserved.