CD24 MEDIATES ROLLING OF BREAST-CARCINOMA CELLS ON P-SELECTIN

P-selectin mediates rolling of neutrophils and other leukocytes on act ivated endothelial cells and platelets through binding to P-selectin g lycoprotein ligand-l (PSGL-1). Certain PSGL-1 negative tumor cell line s can bind P-selectin under static conditions through the GPI-linked s urface mucin, CD24, but the physiological significance of this interac tion and whether it can occur under flow conditions is not known. Here , we show that CD24(+) PSGL-1(-) KS breast carcinoma cells attach to a nd roll on recombinant P-selectin under a continuous wall shear stress , although at a lower density and higher velocity than CD24(+) PSGL-1( +) cells, such as HL-60. Adding excess soluble CD24 or removing CD24 f rom the cell surface with phosphatidylinositol-phospholipase C (PI-PLC ) significantly reduced KS cell rolling on P-selectin. The ability of KS cells to roll on P-selectin was positively correlated with the CD24 expression level. Comparison with three other CD24(+) cell. Lines est ablished that expression of sialyl-Lewis(x) antigen was also necessary for CD24-mediated rolling on P-selectin. CD24 purified from KS cells supported rolling of P-selectin transfectants, but not L-selectin tran sfectants. Finally, KS cells rolled on vascular endothelium in vivo in a P-selectin-dependent manner. Together our data show that CD24 serve s as a ligand for P-selectin under physiological now conditions. Inter action of tumor cells with P-selectin via CD24 may be an important adh esion pathway in cancer metastasis.-Aigner, S., Ramos, C. L., Hafezi-M oghadam, A., Lawrence, M. B., Friederichs, J., Altevogt, P., and Ley, K. CD24 mediates rolling of breast carcinoma cells on P-selectin.