RESUMO
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.
Assuntos
Molécula 1 de Adesão Intercelular/metabolismo , Mucina-1 , Oligopeptídeos/metabolismo , Sequências de Repetição em Tandem , Adenocarcinoma/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos/farmacologia , Sítios de Ligação , Ligação Competitiva , Feminino , Humanos , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Dados de Sequência Molecular , Oligopeptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
The MUC 1 mucin is expressed on normal breast epithelium and in 90% of breast cancers. We report here that tumor-associated MUC1 is a ligand for intercellular adhesion molecule 1 (ICAM-1). Antibodies to ICAM-1 and to MUC1 inhibited adhesion of human and transfected mouse MUC1-positive cell lines to human umbilical vein endothelial cell monolayers and immobilized recombinant human ICAM-1-immunoglobulin fusion protein. Purified MUC1 pretreatment of recombinant human ICAM-1 was an equally effective inhibitor of adhesion. The interaction between MUC1 and ICAM-1 may be critical to the process of bloodborne metastases in breast cancer.
