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.

• Authors: Insug O, Laszlo Otvos, Thomas Kieber-Emmons, Magdalena Blaszczyk-Thurin
• Journal: Peptides (Peptides) Vol. 23 Issue 5 Pg. 999-1010 (May 2002) ISSN: 0196-9781 [Print] United States
• PMID: 12084533 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• CA-19-9 Antigen
• E-Selectin
• Gangliosides
• Ligands
• Peptides
• sialyl Le(a) ganglioside

Topics

• Amino Acid Sequence
• Amino Acid Substitution
• Animals
• Antibodies, Monoclonal (immunology)
• Antibody Affinity
• Binding, Competitive
• CA-19-9 Antigen
• Circular Dichroism
• Disease Models, Animal
• E-Selectin (genetics, metabolism)
• Female
• Gangliosides (antagonists & inhibitors, chemistry, immunology, metabolism)
• Gene Deletion
• Ligands
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Mice
• Mice, Knockout
• Models, Biological
• Molecular Mimicry
• Molecular Sequence Data
• Neoplasm Metastasis (drug therapy, pathology)
• Peptides (chemistry, metabolism, pharmacology, therapeutic use)
• Protein Structure, Secondary