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 Galbeta(1-4)Fucalpha(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 ) approximately 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.

• Authors: María Teresa Elola, Mariana Isabel Capurro, María Marcela Barrio, Peter J Coombs, Maureen E Taylor, Kurt Drickamer, José Mordoh
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 101 Issue 2 Pg. 161-74 (Jan 2007) ISSN: 0167-6806 [Print] Netherlands
• PMID: 16850248 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Lectins, C-Type
• Lewis X Antigen

Topics

• Antibodies, Monoclonal (immunology, pharmacology)
• Blotting, Western
• Breast Neoplasms (metabolism)
• Cell Adhesion (physiology)
• Cell Line, Tumor
• Endothelial Cells (metabolism)
• Endothelium, Vascular (metabolism)
• Female
• Flow Cytometry
• Fluorescent Antibody Technique
• Humans
• Lectins, C-Type
• Lewis X Antigen (immunology, metabolism)
• Neutrophils (metabolism)