Macrophage-tumour cell interactions: identification of MUC1 on breast cancer cells as a potential counter-receptor for the macrophage-restricted receptor, sialoadhesin.
In many carcinomas, infiltrating macrophages are commonly found closely associated with tumour cells but little is known concerning the nature or significance of adhesion molecules involved in these cellular interactions. Here we demonstrate in primary human breast cancers that sialoadhesin (Sn), a macrophage-restricted adhesion molecule, is frequently expressed on infiltrating cells that often make close contact with breast carcinoma cells. To determine whether Sn could act as a specific receptor for ligands on breast cancer cell lines, binding assays were performed with a recombinant form of the protein fused to the Fc portion of human immunoglobulin G1 (IgG1) (Sn-Fc). Sn-Fc was found to bind specifically and in a sialic acid-dependent manner to the breast cancer cell lines MCF-7, T47.D and BT-20 both in solid- and solution-phase binding assays. To investigate the nature of the sialoglycoproteins recognized by Sn on breast cancer cells, MCF-7 cells were labelled with [6-3H]glucosamine. Following precipitation with Sn-Fc, a major band of approximately 240000 MW was revealed, which was shown in reprecipitation and Western blotting experiments to be the epithelial mucin, MUC1.
Nath
D
D
ICRF Laboratories, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, UK.
Hartnell
A
A
Happerfield
L
L
Miles
D W
DW
Burchell
J
J
Taylor-Papadimitriou
J
J
Crocker
P R
PR
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D018396:Mucin-1 / Q000032:analysis*; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D063267:Sialic Acid Binding Ig-like Lectin 1; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D018396:Mucin-1; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1