CD24 mediates rolling of breast carcinoma cells on P-selectin.
P-selectin mediates rolling of neutrophils and other leukocytes on activated endothelial cells and platelets through binding to P-selectin glycoprotein ligand-1 (PSGL-1). Certain PSGL-1 negative tumor cell lines can bind P-selectin under static conditions through the GPI-linked surface mucin, CD24, but the physiological significance of this interaction and whether it can occur under flow conditions is not known. Here, we show that CD24+ PSGL-1- KS breast carcinoma cells attach to and 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 from 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 established 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 transfectants. Finally, KS cells rolled on vascular endothelium in vivo in a P-selectin-dependent manner. Together our data show that CD24 serves as a ligand for P-selectin under physiological flow conditions. Interaction of tumor cells with P-selectin via CD24 may be an important adhesion pathway in cancer metastasis.
Aigner
S
S
Tumor Immunology Program, German Cancer Research Center, Heidelberg.
Ramos
C L
CL
Hafezi-Moghadam
A
A
Lawrence
M B
MB
Friederichs
J
J
Altevogt
P
P
Ley
K
K
D015703:Antigens, CD / Q000302:isolation & purification / Q000502:physiology*; D001943:Breast Neoplasms / Q000503:physiopathology*; D051927:CD24 Antigen; D002448:Cell Adhesion; D002465:Cell Movement; D002846:Chromatography, Affinity; D005260:Female; D006031:Glycosylation; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins; D019007:P-Selectin / Q000502:physiology*; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; D008562:Membrane Glycoproteins; D019007:P-Selectin