Lewis X antigen mediates adhesion of human breast carcinoma cells to activated endothelium. Possible involment of the scavenger receptor C-type lectin.

ELOLA, M. T.; CAPURRO, M. I.; BARRIO, M. M.; COOMBS, P. J.; TAYLOR, M. E.; DRICKAMER, K.; MORDOH, J.

BREAST CANCER RESEARCH AND TREATMENT

Springer

Lugar: Heidelberg; Año: 2006 vol. 101 p. 161 - 174

0167-6806

Lewis x (Lex , CD15), also known as SSEA-1 (stage specific embryonic antigen-1), is a trisaccharide with the structure Gal-beta(1-4)Fuc-alpha(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 Mr ~ 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.