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

Selectins, a family of cell adhesion molecules, bind to sialylated and fucosylated carbohydrates, such as sialyl Lewis(x) (SLe(x)) 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 SLe(x), This finding was bolstered by reduced expression of alpha-1,3-fucosyltransferase VII mRNA and by absence of the cell surface expression of P-selectin glycoprotein ligand-l, Instead, they expressed heparan sulfate-like proteoglycans on their cell surfaces. Treatment with beta-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, me found that P-selectin could bind specifically to human tongue squamous cancer Tca-8113 cells, which had negative staining of SLe(x) but positive staining of heparan sulfates, Both beta-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.