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

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Abstract

Lewis x (Lex, 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 Lex 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-Lex mAbs (FC-2.15 and MCS-1) on this adhesion. We also analyzed the cytolysis of Lex+-cells induced by anti-Lex 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 Lex-dependent PMN interaction with HUVEC. Although both anti-Lex 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 Lex-trisaccharide, interacts with specific glycoproteins of M r␣∼␣28 kD and 10 kD from MCF-7 cells. The interaction between Lex+-cancer cells and vascular endothelium is a potential target for cancer treatment.

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Abbreviations

Ags:

antigens

C′:

complement

CD:

Cluster of Differentiation

CDC:

complement-dependent cytotoxicity

CEA:

carcinoembryonic antigen

CEA-CAM-1:

carcinoembryonic antigen-related cell adhesion molecule 1

DC:

dendritic cell

DC-SIGN:

dendritic cell-specific [intercellular adhesion molecule]-3- grabbing nonintegrin

2dGlc:

2-deoxy-d-glucose

FACS:

Fluorescence-activated cell sorting

FITC:

fluorescein isothiocyanate

fMLP:

N-formyl-methionyl-leucyl-phenylalanine

HUVEC:

human umbillical vein endothelial cells

IAA:

iodoacetic acid

ICAM-3:

intercellular adhesion molecule-3

LPS:

lipopolysaccharide

Lex :

Lewis x

Galβ1–4(Fucα1–3) GlcNAc:

Lewis x

Lea :

Lewis a

Galβ1–3(Fucα1–4) GlcNAc:

Lewis a

sLex :

Silayl-Lewis x

NeuAcα2–3 Galβ1– 4(Fucα1–3) GlcNAc:

Silayl-Lewis x

mAb:

monoclonal antibody

PBS:

phosphate buffered saline

PMN:

polymorphonuclear neutrophils

PMSF:

phenyl-methyl-sulfonyl-fluoride

SRCL:

scavenger receptor C-type lectin

SSEA-1:

stage specific embryonic antigen 1

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Acknowledgements

This work has been supported by grants from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), Fundación Sales, Fundación para la Investigación y Prevención del Cancer (FUCA), Fundación Pedro F. Mosoteguy, Fundación María Calderón de la Barca, Argentina, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council. JM and MTE are members of CONICET. We are grateful to the Obstetric Department, Hospital Rivadavia, Argentina, for providing umbilical cords from normal volunteers. We also acknowledge the Hematology and Obstetric Departments, Hospital Naval Pedro Mallo, Argentina, for the provision of blood/human serum, and umbilical cords, respectively, from normal volunteers.

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Authors and Affiliations

  1. Fundación Instituto Leloir, Patricias Argentinas 435 (1405), Buenos Aires, Argentina

    María Teresa Elola & José Mordoh

  2. Division of Molecular and Cell Biology, Sunnybrook and Women’s College Health Sciences Center and Department of Medical Biophysics, University of Toronto, Ontario, Canada

    Mariana Isabel Capurro

  3. Centro de Investigaciones Oncológicas – FUCA, Zabala 2836, Buenos Aires, Argentina

    María Marcela Barrio & José Mordoh

  4. Division of Molecular Biosciences, Biochemistry Building, Imperial College, London , SW7 2AZ, United Kingdom

    Peter J. Coombs, Maureen E. Taylor & Kurt Drickamer

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  1. María Teresa Elola
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  2. Mariana Isabel Capurro
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  3. María Marcela Barrio
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  4. Peter J. Coombs
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  7. José Mordoh
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Correspondence to José Mordoh.

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Elola, M.T., Capurro, M.I., Barrio, M.M. et al. Lewis x Antigen Mediates Adhesion of Human Breast Carcinoma Cells to Activated Endothelium. Possible Involvement of the Endothelial Scavenger Receptor C-type Lectin. Breast Cancer Res Treat 101, 161–174 (2007). https://doi.org/10.1007/s10549-006-9286-9

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