P-SELECTIN-DEPENDENT ADHESION OF HUMAN CANCER-CELLS - REQUIREMENT FOR COEXPRESSION OF A PSGL-1-LIKE CORE PROTEIN AND THE GLYCOSYLATION PROCESS FOR SIALOSYL-LE(X) OR SIALOSYL-LE(A)

Abstract

We studied the cell surface expression of sialosyl-Le(x) (SLe(x)) and sialosyl-Le(a) (SLe(a)) and its correlation with E-selectin- and P-selectin-dependent cell adhesion, employing 12 human cancer cell lines derived from solid tumors and 2 myelogenic leukemic cell lines, HL60 and U937. Among all the cell lines tested, there was a clear correlation between E-selectin-dependent adhesion and degree of SLe(x) and SLe(a) expression. None of the cell lines derived from solid tumors bound significantly to P-selectin, but leukemic cell lines HL60 and U937 bound strongly to P-selectin. The cDNA clone encoding P-selectin glycoprotein ligand-1 (PSGL-1) was transfected into colonic cancer HRT18 and lung cancer PC3 cells, which express SLe(x) and SLe(a) but normally do not bind to P-selectin, although they do bind to E-selectin. The resulting transfectants bound strongly to P-selectin and equally well to E-selectin. A crude mucin fraction extracted from pooled human colonic cancer tissue bound to E-selectin but not to P-selectin. We conclude that tumor cell adhesion to P-selectin is highly dependent on expression of a specific core protein which appropriately assembles a specific carbohydrate to present to P-selectin. In contrast, E-selectin binds promiscuously to various types of SLe(x) and SLe(a) epitopes presented at the cell surface through N-linked, O-linked, or lipid-linked structures.