Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated type I carbohydrate chain.
Endothelial leukocyte adhesion molecule-1 (ELAM-1) has been determined to be the mediator of adhesion of colon carcinoma cells to interleukin-1 (IL-1)-activated endothelial cells. To identify ELAM-1 ligand in colon carcinoma cells, we have screened a series of 11 monoclonal antibodies directed to these cells and found that only one MBr8 was able to inhibit the IL-1-induced increment in adhesion of HT29 and of SW948 colon carcinoma lines to endothelial cells. In contrast, MBr8 did not bind to polymorphonuclear cells, monocytes, and lymphocytes and did not inhibit polymorphonuclear adhesion to IL-1-activated endothelial cells. As expected, an ELAM-1 monoclonal antibody strongly inhibited IL-1 induced increment of adhesion of HT29, SW948, and polymorphonuclear cells. As negative control, MG63 osteosarcoma cells were used. These cells adhere more efficiently to IL-1 activated endothelial cells but MBr8 and ELAM-1 monoclonal antibodies did not affect their adhesion. The effect of MBr8 was also tested in an experimental system in vivo. As described previously, radiolabeled HT29 cell retention in the lung of nude mice was increased in animals given IL-1. MBr8 administration to nude mice or pretreatment of tumor cells with it inhibited this effect. These data suggest that cell adhesion to ELAM-1 might be mediated by different, cell type specific, sugar ligands.
Mario Negri Institute for Pharmacological Research, Milano, Italy.
E
E
Dejana
I
I
Martin-Padura
D
D
Lauri
S
S
Bernasconi
M R
MR
Bani
A
A
Garofalo
R
R
Giavazzi
J
J
Magnani
A
A
Mantovani
S
S
Menard
D000911:Antibodies, Monoclonal; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007983:Lewis Blood Group Antigens