Lewis x antigen mediates adhesion of human breast carcinoma cells to activated endothelium. Possible involvement of the endothelial scavenger receptor C-type lectin.
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.
Elola
María Teresa
MT
Fundación Instituto Leloir, Patricias Argentinas 435 (1405), Buenos Aires, Argentina.
Capurro
Mariana Isabel
MI
Barrio
María Marcela
MM
Coombs
Peter J
PJ
Taylor
Maureen E
ME
Drickamer
Kurt
K
Mordoh
José
J
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D037181:Lectins, C-Type; D016256:Lewis X Antigen / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism
D000911:Antibodies, Monoclonal; D037181:Lectins, C-Type; D016256:Lewis X Antigen