Macrophage–tumour cell interactions: identification of MUC1 on breast cancer cells as a potential counter‐receptor for the macrophage‐restricted receptor, sialoadhesin

Abstract

SUMMARYIn 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 #240 000 MW was revealed, which was shown in reprecipitation and Western blotting experiments to be the epithelial mucin, MUC1.

The Relative Activities of the C2GnT1 and ST3Gal-I Glycosyltransferases Determine O-Glycan Structure and Expression of a Tumor-associated Epitope on MUC1

“…Whether the increased expression of ST3Gal-I, which we have identified in breast cancers, affects function, possibly by affecting cell interactions, is unclear. Certainly core 1 carrying a sialic acid in ␣2,3 linkage is a major ligand for sialoadhesin, and MUC1 carrying such glycans interacts well with this sialic acid binding protein found on macrophages, which can be found as infiltrates in a proportion of breast cancers (37).…”

Ectopic Expression of PA2.26 Antigen in Epidermal Keratinocytes Leads to Destabilization of Adherens Junctions and Malignant Progression

“…Mucin-type membrane glycoproteins have been shown to exhibit both anti-adhesive and cell-cell adhesive properties (Baumhueter et al, 1994;Gendler and Spicer, 1995;Nath et al, 1999). The anti-adhesive function of large transmembrane mucins, such as episialin (MUC1), epiglycanin, and sialomucin, is attributable to their masking cell adhesion receptors because of their large extended ectodomains and to the repulsive forces provided by sialic acid (Kemperman et al, 1994;Komatsu et al, 1997;Wesseling et al, 1996).…”

Binding of the Sialic Acid-binding Lectin, Siglec-9, to the Membrane Mucin, MUC1, Induces Recruitment of β-Catenin and Subsequent Cell Growth

“…This extended structure is expected to act as a particularly effective scaffold for the presentation of oligosaccharide chains to lectins, thereby promoting interactions between cancer cells and appropriate lectinexpressing cells. It has been reported that MUC1 is a natural ligand of endogenous Siglec-1 (14) and galectin-3 (15,16) and that the binding of galectin-3 increases the adhesion between cancer cells and endothelial cells and the aggregation of tumor cells. However, these studies provided no insights to the downstream signaling by MUC1 after binding of these lectins.…”