CD24, A MUCIN-TYPE GLYCOPROTEIN, IS A LIGAND FOR P-SELECTIN ON HUMAN TUMOR-CELLS

P-selectin (CD62P) is a Ca2+-dependent endogenous lectin that can be e xpressed 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 lig and(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 glycosylphosph atidylinositol-linked cell surface molecule on human neutrophils, pre B lymphocytes, and many tumors can promote binding to P-selectin. Late x beads coated with purified CD24 from the two carcinoma cell sines bu t also neutrophils could bind specifically to P-selectin-lgG. The bind ing was dependent on divalent cations and was abolished by treatment w ith O-sialoglycoprotein endopeptidase but not endoglycosidase F or sia lidase. The beads were stained with a monoclonal antibody (MoAb) to CD 57 (HNK-1 carbohydrate epitope) but did not react with MoAbs against t he sialylLe(x/a) epitope, The carcinoma cells and CD24-beads derived f rom these cells could bind to activated platelets or P-selectin transf ected Chinese hamster ovary cells (P-CHO) in a P-selectin-dependent ma nner and this binding was blocked by soluble CD24. Transfection of hum an adenocarcinoma cells with CD24 enhanced the P-selectin-dependent bi nding to activated platelets, Treatment of the carcinoma cells or the CD24 transfectant with phosphatidylinositol-specific phospholipase C r educed CD24 expression and P-selectin-lgG 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. (C) 1997 by The American Society of H ematology.