title: Vascular endothelial cells that express dystroglycan are involved in angiogenesis.
abstract: We have earlier shown that dystroglycan (DG) is a lamininbinding protein and as such is a cell adhesion molecule. DG is a heterodimer of alpha and beta DG subunits. beta-dystroglycan (betaDG) is the membrane spanning subunit, whereas the alpha subunit is bound to the extracellular domain of betaDG. To study physiological function of the protein, we expressed full-length DG (FL-DG) and the cytoplasmic domain of betaDG (deltabetaDG) in bovine aortic endothelial cells (BAE) and examined their effects on cell adhesion, migration, proliferation and tube formation. FL-DG enhanced adhesion of BAE to laminin-1, whereas deltabetaDG inhibited it. Cell migration was inhibited by overexpressing deltabetaDG in these cells, although it was not affected by FL-DG overexpression. In a proliferation assay, FL-DG decreased the growth rate, and it also caused cells to extensively spread. deltabetaDG caused opposite effects; it increased the growth rate and reduced the cell surface area. In a tube formation assay on Matrigel, FL-DG caused an obvious inhibition, whereas deltabetaDG accelerated tube formation. These results suggest a potential role of endothelial dystroglycan in the control of angiogenesis. Anti-betaDG immunohistochemistry indicated increased expression of DG in vascular endothelial cells within malignant tumors. By contrast, the antibody failed to stain endothelial cells in normal tissues. In cultured BAE, the level of betaDG was low in serum-deprived quiescent cells and was upregulated in proliferating cells. Our results suggest that the expression of DG in endothelial cells is under a dynamic regulation and may play a role in angiogenesis.
authors.affiliation: Center for Cardiovascular Research, University of Rochester School of Medicine and Dentistry, Rochester NY 14642-8679, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Haruaki
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Yukisato
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Keigi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Tomoh
authors.initials: T
authors.lastname: Masaki
mesh_terms: D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism*; D004338:Drug Combinations; D049030:Dystroglycans; D004730:Endothelium, Vascular / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D004338:Drug Combinations; D007797:Laminin; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C121346:laminin 1; C059485:matrigel; D049030:Dystroglycans; D003094:Collagen