Tumor cells interact with endothelial cells during both intraand extravasation. Understanding how these interactions are modulated could lead to the development of ways to alter the metastatic potential of tumor cells. Three pancreatic cancer cell lines, SW 1990, CAPAN-2 and PANC-I, were examined for their ability to bind to the endothelial cell adhesion molecule E-selectin (ELAM-I). SW I990 cells exhibited highest binding, highest surface expression of the carbohydrate antigens sialylated Lewis" (sLea) and sialylated LewisX (sLex) and released the most high m.w. sLea and sLe" antigens. Expression of rLea and sLex antigens and binding to E-selectin were reduced by pre-treatment of SW I990 cells with the 0-linked glycosylation inhibitor benzyl-a-GalNAc but not with the N-linked glycosylation inhibitor tunicamycin. Expression of peptide epitopes associated with MUC I apornucins was increased by benzyl-a-GalNAc. Cell binding was greatly reduced by rnucins purified from SW I990 xenografts and by an antibody against sLea. An antibody against sLex had a much less marked effect. Sera from pancreatic cancer patients reduced SW I990 cell binding to E-selectin but sera from normals did not. The degree of inhibition was related to the sLex level in the sample. When cancer serum was separated by column chromatography on Sephacryl S-400, the void volume fractions contained most of the sLea and sLex antigens and most of the inhibitory activity to E-selectin binding. Differences in the relative availability of sLea and sLex ligands on serum molecules and on the SW1990 cell surface may account for the differences between antibody and serum inhibition results. Thus SWI990 cell adhesion to Eselectin is mediated by ligands on rnucinous glycoproteins, and adhesion can be inhibited by mucins, high blood levels of sLex and reduction of cellular 0-linked glycosylation.