Binding of CD157 protein to fibronectin regulates cell adhesion and spreading

CD157/BST-1 behaves both as an ectoenzyme and signaling receptor and is an important regulator of leukocyte trafficking and ovarian cancer progression. However, the molecular inter- actions underpinning the role of CD157 in these processes remain obscure. The biological functions of CD157 and its part- nership with members of the integrin family prompted us to assumetheexistenceofadirectinteractionbetweenCD157and anunknowncomponentoftheextracellularmatrix.Usingsolid- phase binding assays and surface plasmon resonance analysis, we demonstrated that CD157 binds fibronectin with high affin- itywithinitsheparin-bindingdomains1and2.Furthermore,we found that CD157 binds to other extracellular matrix proteins containing heparin-binding domains. Finally, we proved that the CD157-fibronectin interaction occurs with living cells, where it elicits CD157-mediated cell responses. Indeed, knock- down of CD157 in Met-5A mesothelial cells changed their morphology and cytoskeleton organization and attenuated theactivationofintracellularsignalingpathwaystriggeredby fibronectin. This led to impaired cell spreading and adhesion to selected extracellular matrix proteins. Collectively, these find- ings indicate a central role of CD157 in cell-extracellular matrix interactionsandmakeCD157anattractivetherapeutictargetin inflammation and cancer.