P-selectin Ligands On Human Cancer Cells

Stimulated endothelial cells and activated platelets express P-selectin, which reacts P-selectin glycoprotein ligand-1 (PSGL-1) expressing on most of leukocytes for leukocyte rolling on the endothelial cell and heterotypic aggregation of the activated platelets on leukocytes. P-selectin also binds to several cancer cells in vitro and promotes the growth and metastasis of human colon carcinoma in vivo. The P-selectin/PSGL-1 interaction requires tyrosine sulfation and sialylated and fucosylated carbohydrates designated as Slex. Although some cancer cells express Slex or CD24, it is unknown which molecules mediate P-selectin binding for most other cancer cells. In this study, we show that: (1) Many types of non-blood borne, epithelial-like human cancer cells can bind to P-selectin; (2) Heparan sulfate-like proteoglycans can mediate adhesion of human malignant melanoma A375 cells and human tongue squamous cancer Tca8113 cells to P-selectin under flow; (3) Sulfation is essential for adhesion of human salivary gland carcinoma Acc-M cells and breast carcinoma ZR-75-30 cells to P-selectin; (4) Tyrosine sulfation is required for adhesion of breast carcinoma ZR-75-30 cells to P-selectin.