title: CD24, a mucin-type glycoprotein, is a ligand for P-selectin on human tumor cells.
abstract: P-selectin (CD62P) is a Ca2+-dependent endogenous lectin that can be expressed by vascular endothelium and platelets. The major ligand for P-selectin on leukocytes is P-selectin glycoprotein ligand-1 (PSGL-1). P-selectin can also bind to carcinoma cells, but the nature of the ligand(s) on these cells is unknown. Here we investigated the P-selectin binding to a breast and a small cell lung carcinoma cell line that are negative for PSGL-1. We report that CD24, a mucin-type glycosylphosphatidylinositol-linked cell surface molecule on human neutrophils, pre B lymphocytes, and many tumors can promote binding to P-selectin. Latex beads coated with purified CD24 from the two carcinoma cell lines but also neutrophils could bind specifically to P-selectin-IgG. The binding was dependent on divalent cations and was abolished by treatment with O-sialoglycoprotein endopeptidase but not endoglycosidase F or sialidase. The beads were stained with a monoclonal antibody (MoAb) to CD57 (HNK-1 carbohydrate epitope) but did not react with MoAbs against the sialylLe(x/a) epitope. The carcinoma cells and CD24-beads derived from these cells could bind to activated platelets or P-selectin transfected Chinese hamster ovary cells (P-CHO) in a P-selectin-dependent manner and this binding was blocked by soluble CD24. Transfection of human adenocarcinoma cells with CD24 enhanced the P-selectin-dependent binding to activated platelets. Treatment of the carcinoma cells or the CD24 transfectant with phosphatidylinositol-specific phospholipase C reduced CD24 expression and P-selectin-IgG binding concomitantly. These results establish a role of CD24 as a novel ligand for P-selectin on tumor cells. The CD24/P-selectin binding pathway could be important in the dissimination of tumor cells by facilitating the interaction with platelets or endothelial cells.
authors.affiliation: Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
authors.forename: S
authors.initials: S
authors.lastname: Aigner
authors.forename: Z M
authors.initials: ZM
authors.lastname: Sthoeger
authors.forename: M
authors.initials: M
authors.lastname: Fogel
authors.forename: E
authors.initials: E
authors.lastname: Weber
authors.forename: J
authors.initials: J
authors.lastname: Zarn
authors.forename: M
authors.initials: M
authors.lastname: Ruppert
authors.forename: Y
authors.initials: Y
authors.lastname: Zeller
authors.forename: D
authors.initials: D
authors.lastname: Vestweber
authors.forename: R
authors.initials: R
authors.lastname: Stahel
authors.forename: M
authors.initials: M
authors.lastname: Sammar
authors.forename: P
authors.initials: P
authors.lastname: Altevogt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000502:physiology; D001943:Breast Neoplasms; D051927:CD24 Antigen; D018959:CD57 Antigens / Q000032:analysis / Q000378:metabolism; D016466:CHO Cells; D002448:Cell Adhesion; D002846:Chromatography, Affinity; D006224:Cricetinae; D017931:DNA Primers; D000939:Epitopes / Q000032:analysis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D008024:Ligands; D008175:Lung Neoplasms; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009077:Mucins / Q000096:biosynthesis*; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015539:Platelet Activation; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; D018959:CD57 Antigens; D017931:DNA Primers; D000939:Epitopes; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D009077:Mucins; D019007:P-Selectin; C084882:P-selectin ligand protein