Sialyl Lewis X-dependent lung colonization of B16 melanoma cells through a selectin-like endothelial receptor distinct from E- or P-selectin.
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.
Zhang
Jianing
J
Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA.
Nakayama
Jun
J
Ohyama
Chikara
C
Suzuki
Masami
M
Suzuki
Atsushi
A
Fukuda
Minoru
M
Fukuda
Michiko N
MN
D000818:Animals; D019040:E-Selectin / Q000096:biosynthesis / Q000502:physiology; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018716:Molecular Mimicry; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D009844:Oligosaccharides / Q000037:antagonists & inhibitors / Q000502:physiology*; D019007:P-Selectin / Q000096:biosynthesis / Q000502:physiology; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D000080506:Sialyl Lewis X Antigen
D019040:E-Selectin; D009842:Oligopeptides; D009844:Oligosaccharides; D019007:P-Selectin; D018000:Receptors, Peptide; D000080506:Sialyl Lewis X Antigen; C404394:isoleucyl-glutamyl-leucyl-leucyl-glutaminyl-alanyl-arginine