Lysosomal membrane glycoprotein (lamp)-1 and lamp-2 are the most abundant glycoproteins within the lysosomal membrane. A small amount of lamp-1 and lamp-2 molecules, however, can be present on the cell surface. We have shown previously that highly metastatic colonic carcinoma L4 cells express more lamp-1 and lamp-2 on the cell surface than low metastatic SP cells (Saitoh, O., Wang, W.-L., Lotan, R., and Fukuda, M. (1992) J. Biol. Chem. 267, 5700-5711). Since lamp-1 and lamp-2 are the major carriers for poly-N-acetyllactosamines that are able to display sialyl-Le(x) termini, we sought to determine if an increased amount of lamp-1 on the cell surface would lead to increased expression of cell surface sialyl-Le(x) determinants and to the increased adhesion of those cells to E-selectin. Expression of increased amounts of lamp-1 on the cell surface was achieved either by overexpression of lamp-1 or by expressing a mutant lamp-1 molecule preferentially at the plasma membrane, rather than in lysosomes. Cells that express variable amounts of cell surface lamp-1 were tested for their adhesion to activated endothelial cells or E-selectin expressing Chinese hamster ovary cells. The results clearly show that the extent of adhesion to E-selectin and cell surface sialyl-Le(x) determinants is proportional to the amount of cell surface lamp-1. Moreover, it was demonstrated that such adhesion can be inhibited by soluble lamp-1 generated from Chinese hamster ovary cells expressing sialyl-Le(x) structures. These results indicate that lamp-1 can efficiently present ligands for E-selectin and at the same time can be a useful reagent for inhibition of E-selectin (and possibly P-selectin)-mediated interaction.