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 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 alpha-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 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, 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 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.
Ma
Y Q
YQ
Shanghai Institute of Cell Biology, Chinese Academy of Sciences, China.
Geng
J G
JG
D001667:Binding, Competitive / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D006027:Glycosides / Q000494:pharmacology; D018922:HL-60 Cells; D019812:Heparan Sulfate Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D019763:Heparin Lyase / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008565:Membrane Proteins / Q000096:biosynthesis; D019007:P-Selectin / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012212:Rheology; D014407:Tumor Cells, Cultured
D006027:Glycosides; D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins; D019007:P-Selectin; C010807:xylosides; D006493:Heparin; D019763:Heparin Lyase