Heparan sulfate-like proteoglycans mediate adhesion of human malignant melanoma A375 cells to P-selectin under

Selectins, a family of cell adhesion molecules, bind to sialylated and fucosylated carbohydrates, such as sialyl Lewisx (SLex) and its derivatives, as their minimal recognition motif. Here we report that P-selectin bound to human malignant melanoma A375 cells and mediated their adhesion under flow. However, probing with a specific Ab failed to detect any apparent expression of SLex. This finding was bolstered by reduced expression of a-1,3-fucosyltransferase VII mRNA and by absence of the cell surface expression of P-selectin glycoprotein ligand-1. Instead, they expressed heparan sulfate-like proteoglycans on their cell surfaces. Treatment with b-D-xyloside (a proteoglycan biosynthesis inhibitor) or heparinases could reduce the binding of these cells to P-selectin. In the competition assays, heparin, but not other proteoglycans, could abolish the P-selectin recognition. Further, we found that P-selectin could bind specifically to human tongue squamous cancer Tca-8113 cells, which had negative staining of SLex but positive staining of heparan sulfates. Both b-D-xyloside and heparinases could reduce the binding of P-selectin to Tca-8113 cells. Our results thus indicate that heparan sulfate-like proteoglycans can mediate adhesion of certain types of non-blood borne, “epithelial-like ” human cancer cells to P-selectin. The Journal of Immunology, 2000, 165: 558–565. L eukocyte-endothelial cell interactions are mediated by atleast four families of cell adhesion molecules. They areselectins (CD62), selectin ligands, integrins, and the IgG superfamily of cell adhesion molecules. The selectin family in-cludes L-selectin (CD62L), a constitutively expressed receptor on most leukocytes; E-selectin (CD62E), a cytokine-inducible mole