MUC1 mucin core protein binds to the domain 1 of ICAM-1.
BACKGROUND
MUC1 is aberrantly expressed on a variety of epithelial tumors. We have reported that MUC1 plays important roles in separation from primary site, invasion into the stromal tissue, and protection from immune responses. The aim of this study is to determine the precise binding of MUC1 to intercellular adhesion molecule 1 (ICAM-1) that accelerates the cancer metastasis.


METHODS
A cell aggregation assay between MUC1 cDNA transfectants and ICAM-1 expressing cells was employed. An anti-MUC1 antibody, anti-ICAM-1 antibody or synthetic peptide of MUC1 core protein was added to the assay to inhibit the cell aggregation.


RESULTS
MUC1 transfectants showed a significantly higher aggregation rate compared to the control cells. This aggregation was further enhanced by the inhibition of O-glycan biosynthesis. It was inhibited by either an anti-MUC1 antibody recognizing the tandem repeat domain of MUC1 core protein or an anti-ICAM-1 antibody identifying domain 1. It was also inhibited by a synthetic MUC1 peptide of 40 amino acids corresponding to two tandem repeats.


CONCLUSIONS
The results revealed that a tandem repeat domain of MUC1 mucin core protein binds to domain 1 of ICAM-1, suggesting a potential role of MUC1- ICAM-1 interaction in the metastasis of epithelial tumors.
Hayashi
T
T
First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan. Toshiaki_Hayashi@dfci.harvard.edu
Takahashi
T
T
Motoya
S
S
Ishida
T
T
Itoh
F
F
Adachi
M
M
Hinoda
Y
Y
Imai
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites; D002277:Carcinoma / Q000276:immunology* / Q000503:physiopathology; D002449:Cell Aggregation / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000503:physiopathology; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000494:pharmacology; D018396:Mucin-1 / Q000276:immunology* / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000276:immunology*; D020080:Tandem Repeat Sequences; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D018396:Mucin-1; D018799:Intercellular Adhesion Molecule-1