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 α andβ DG subunits. β-dystroglycan (βDG) is the membrane spanning subunit, whereas the α subunit is bound to the extracellular domain ofβDG. To study physiological function of the protein, we expressed full-length DG (FL-DG) and the cytoplasmic domain of βDG(ΔβDG) 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 ΔβDG inhibited it. Cell migration was inhibited by overexpressing ΔβDG 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. ΔβDG 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 ΔβDG accelerated tube formation. These results suggest a potential role of endothelial dystroglycan in the control of angiogenesis. Anti-βDG 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 ofβDG 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.