title: Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix.
abstract: The proteoglycan (PG) on the surface of NMuMG mouse mammary epithelial cells consists of at least two functional domains, a membrane-intercalated domain which anchors the PG to the plasma membrane, and a trypsin-releasable ectodomain which bears both heparan and chondroitin sulfate chains. The ectodomain binds cells to collagen types I, III, and V, but not IV, and has been proposed to be a matrix receptor. Because heparin binds to the adhesive glycoproteins fibronectin, an interstitial matrix component, and laminin, a basal lamina component, we asked whether the cell surface PG also binds these molecules. Cells harvested with either trypsin or EDTA bound to fibronectin; binding of trypsin-released cells was inhibited by the peptide GRGDS but not by heparin, whereas binding of EDTA-released cells was inhibited only by a combination of GRDS and heparin, suggesting two distinct cell binding mechanisms. In the presence of GRGDS, the EDTA-released cells bound to fibronectin via the cell surface PG. Binding via the cell surface PG was to the COOH-terminal heparin binding domain of fibronectin. In contrast with the binding to fibronectin, EDTA-released cells did not bind to laminin under identical assay conditions. Liposomes containing the isolated intact cell surface PG mimic the binding of whole cells. These results indicate that the mammary epithelial cells have at least two distinct cell surface receptors for fibronectin: a trypsin-resistant molecule that binds cells to the sequence RGD and a trypsin-labile, heparan sulfate-rich PG that binds cells to the COOH-terminal heparin binding domain. Because the cell surface PG binds cells to the interstitial collagens (types I, III, and V) and to fibronectin, but not to basal lamina collagen (type IV) or laminin, we conclude that the cell surface PG is a receptor on epithelial cells specific for interstitial matrix components.
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D003094:Collagen / Q000502:physiology; D004847:Epithelial Cells; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D006493:Heparin / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008081:Liposomes; D008321:Mammary Glands, Animal / Q000166:cytology*; D011485:Protein Binding; D011509:Proteoglycans / Q000502:physiology*; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000502:physiology*; D013499:Surface Properties
chemical_list: D005353:Fibronectins; D007797:Laminin; D008081:Liposomes; D011509:Proteoglycans; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D006493:Heparin; D003094:Collagen