Role of SA-Le(a) and E-selectin in metastasis assessed with peptide antagonist

Abstract

E-selectin ligand Sialyl-Lewis a (SA-Le(a)) carbohydrate is expressed on many carcinomas. Peptide mimicking SA-Le(a) (DLWDWVVGKPAG) was previously selected from a recombinant library by screening with monoclonal antibody (MAb) NS19-9. In this study, the residues critical for interaction with the NS19-9 were mapped using peptide array generated by substitution of various amino acid residues. The replacement of Trp 5 with Phe resulted in a change of peptide's secondary structure and increased binding with MAb and E-selectin, suggesting improved carbohydrate mimicry. Colonization of tumor cells expressing SA-Le(a) was blocked by the peptide and was completely abolished in E-selectin knock out mice. The data suggest the critical role of carbohydrate antigens and E-selectin in metastasis and that peptides mimicking carbohydrate antigens can function as antagonists of this process.