Lewis x Antigen Mediates Adhesion of Human Breast Carcinoma Cells to Activated Endothelium. Possible Involvement of the Endothelial Scavenger Receptor C-type Lectin

Abstract

Lewis x (Le^x, CD15), also known as SSEA-1 (stage specific embryonic antigen-1), is a trisaccharide with the structure Galβ(1–4)Fucα(1–3)GlcNAc, which is expressed on glycoconjugates in human polymorphonuclear granulocytes and various tumors such as colon and breast carcinoma. We have investigated the role of Le^x in the adhesion of MCF-7 human breast cancer cells and PMN to human umbilical endothelial cells (HUVEC) and the effects of two different anti-Le^x mAbs (FC-2.15 and MCS-1) on this adhesion. We also analyzed the cytolysis of Le^x+-cells induced by anti-Le^x mAbs and complement when cells were adhered to the endothelium, and the effect of these antibodies on HUVEC. The results indicate that MCF-7 cells can bind to HUVEC, and that MCS-1 but not FC-2.15 mAb inhibit this interaction. Both mAbs can efficiently lyse MCF-7 cells bound to HUVEC in the presence of complement without damaging endothelial cells. We also found a Le^x-dependent PMN interaction with HUVEC. Although both anti-Le^x mAbs lysed PMN in suspension and adhered to HUVEC, PMN aggregation was only induced by mAb FC-2.15. Blotting studies revealed that the endothelial scavenger receptor C-type lectin (SRCL), which binds Le^x-trisaccharide, interacts with specific glycoproteins of M _r␣∼␣28 kD and 10 kD from MCF-7 cells. The interaction between Le^x+-cancer cells and vascular endothelium is a potential target for cancer treatment.