Abstract
Endothelial carbohydrate binding proteins, E- and P-selectins, are thought to mediate sialyl Lewis A/X-dependent hematogenous cancer metastasis. We tested this hypothesis using sialyl Lewis X-dependent B16 melanoma lung targeting and its inhibition with selectin ligand mimicry peptide, IELLQAR. In E/P-selectin doubly deficient mutant mice, sialyl Lewis X-expressing B16 melanoma cells colonized the lung, and IELLQAR inhibited this colonization. However, tumors grown in E/P-selectin-deficient mice were significantly smaller than those grown in wild-type mice. These results indicate that the IELLQAR peptide receptor expressed in the lung vasculature plays a major role in sialyl Lewis X-dependent cancer cells targeting to the lung.
Publication types
- Research Support, U.S. Gov't, Non-P.H.S.
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Animals
- E-Selectin / biosynthesis
- E-Selectin / physiology
- Lung / metabolism
- Lung Neoplasms / blood supply
- Lung Neoplasms / metabolism
- Lung Neoplasms / prevention & control
- Lung Neoplasms / secondary*
- Melanoma, Experimental / blood supply
- Melanoma, Experimental / prevention & control
- Melanoma, Experimental / secondary*
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Molecular Mimicry
- Neovascularization, Pathologic / metabolism
- Oligopeptides / metabolism
- Oligopeptides / pharmacology*
- Oligosaccharides / antagonists & inhibitors
- Oligosaccharides / physiology*
- P-Selectin / biosynthesis
- P-Selectin / physiology
- Receptors, Peptide / biosynthesis
- Receptors, Peptide / metabolism
- Receptors, Peptide / physiology*
- Sialyl Lewis X Antigen
Substances
- E-Selectin
- Oligopeptides
- Oligosaccharides
- P-Selectin
- Receptors, Peptide
- Sialyl Lewis X Antigen
- isoleucyl-glutamyl-leucyl-leucyl-glutaminyl-alanyl-arginine