MUC1 synthetic peptide inhibition of intercellular adhesion molecule-1 and MUC1 binding requires six tandem repeats.
We reported recently that breast cancer-associated MUC1 is a ligand for intercellular adhesion molecule-1 (ICAM-1; L. H. Regimbald et al., Cancer Res., 56: 4244-4249, 1996). We report here the results of a competitive indirect binding assay to detect the molecular requirements for binding between ICAM-1 and MUC1. The assay involved inhibition of the binding of recombinant human ICAM-1 to a murine breast adenocarcinoma cell line transfected with human MUC1. The addition of a library of human MUC1 synthetic peptides ranging from 9 to 24 amino acids (aa) showed minimal or no inhibition. However, a 120-aa peptide that corresponds to six tandem repeats of the human mucin MUC1 was as effective an inhibitor as purified tumor MUC1 and MUC1 epitope (PDTRPAP)-specific antibody (B27.29). We conclude that the number of MUC1 tandem repeats necessary for an ordered tertiary structure (D. Fontenot et al., Cancer Res., 53: 5386-5394, 1993) is also important for ICAM-1 recognition. These findings are similar to those described recently for MUC1 induction of T-cell anergy (B. Agrawal et al., Nat. Med., 4: 43-49, 1998). This suggests that the anergy induction by MUC1 may be due to ICAM-1 binding by MUC1.
Kam
J L
JL
Department of Laboratory Medicine and Pathology, Cross Cancer Institute, University of Alberta, Edmonton, Canada.
Regimbald
L H
LH
Hilgers
J H
JH
Hoffman
P
P
Krantz
M J
MJ
Longenecker
B M
BM
Hugh
J C
JC
D000230:Adenocarcinoma / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018396:Mucin-1; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D020080:Tandem Repeat Sequences; D014407:Tumor Cells, Cultured
D000906:Antibodies; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D009842:Oligopeptides; D010446:Peptide Fragments; D018799:Intercellular Adhesion Molecule-1