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.
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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)
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Chemical References |
- Antibodies, Monoclonal
- Lectins, C-Type
- Lewis X Antigen
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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)
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