This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fukuda, M. N. Articles by Fukuda, M. Search for Related Content PubMed PubMed Citation Articles by Fukuda, M. N. Articles by Fukuda, M.

A Peptide Mimic of E-Selectin Ligand Inhibits Sialyl Lewis X-dependent Lung Colonization of Tumor Cells¹

The Burnham Institute, Cancer Research Center, La Jolla, California 92037 [M. N. F., C. O., K. L., R. P., E. R., M. F.], and Department of Physiology, Kinki University School of Medicine, Osakasayama, Japan 589-8511 [O. M.]

Selectins bind to carbohydrate ligands in a calcium-dependent manner and play critical roles in host defense and possibly in tumor metastasis. To isolate peptides that mimic E-selectin ligands, we screened a phage peptide library using E-selectin as a target molecule. This attempt unexpectedly failed, probably because the binding affinity of E-selectin to its ligand is low. We then took an approach that is analogous to the isolation of anti-idiotype antibodies and were able to isolate peptides that bound to anticarbohydrate antibodies recognizing E-selectin ligands. These peptides, enriched for their binding to anti-Lewis A antibody, were found to bind to E-, P- and L-selectins in a calcium-dependent manner. Phage harboring the identified peptide IELLQAR and synthetic peptides having the same sequence inhibited the binding of sialyl Lewis X or sialyl Lewis A oligosaccharides to E-selectin. The adhesion of HL-60 and B16 melanoma cells expressing sialyl Lewis X to E-selectin was also inhibited by the phage-displaying IELLQAR peptide. Moreover, i.v. injected IELLQAR peptide inhibited the lung colonization of mouse B16 melanoma and human lung tumor cells expressing sialyl Lewis X. These results demonstrate that it is possible to isolate peptides mimicking carbohydrate ligands by screening the peptides for binding to anticarbohydrate antibodies and then using them to inhibit carbohydrate-dependent experimental tumor metastasis.

This article has been cited by other articles:

				S. Hatakeyama, K. Sugihara, J. Nakayama, T. O. Akama, S.-M. A. Wong, H. Kawashima, J. Zhang, D. F. Smith, C. Ohyama, M. Fukuda, et al. Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells PNAS, March 3, 2009; 106(9): 3095 - 3100. [Abstract] [Full Text] [PDF]

				J. B. Kruskal, A. Azouz, H. Korideck, M. El-Hallak, S. C. Robson, P. Thomas, and S. N. Goldberg Hepatic Colorectal Cancer Metastases: Imaging Initial Steps of Formation in Mice Radiology, June 1, 2007; 243(3): 703 - 711. [Abstract] [Full Text] [PDF]

				K. Sugihara, D. Sugiyama, J. Byrne, D. P. Wolf, K. P. Lowitz, Y. Kobayashi, M. Kabir-Salmani, D. Nadano, D. Aoki, S. Nozawa, et al. Trophoblast cell activation by trophinin ligation is implicated in human embryo implantation PNAS, March 6, 2007; 104(10): 3799 - 3804. [Abstract] [Full Text] [PDF]

				W. Chen, J. Tang, and P. Stanley Suppressors of {alpha}(1,3)fucosylation identified by expression cloning in the LEC11B gain-of-function CHO mutant Glycobiology, March 1, 2005; 15(3): 259 - 269. [Abstract] [Full Text] [PDF]

				J. Zou, V. V. Glinsky, L. A. Landon, L. Matthews, and S. L. Deutscher Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion Carcinogenesis, February 1, 2005; 26(2): 309 - 318. [Abstract] [Full Text] [PDF]

				J. Pan, H. Yeger, and E. Cutz Neuronal Developmental Marker FORSE-1 Identifies a Putative Progenitor of the Pulmonary Neuroendocrine Cell Lineage During Lung Development J. Histochem. Cytochem., December 1, 2002; 50(12): 1567 - 1578. [Abstract] [Full Text] [PDF]

				C. Ohyama, S. Kanto, K. Kato, O. Nakano, Y. Arai, T. Kato, S. Chen, M. N. Fukuda, and M. Fukuda Natural killer cells attack tumor cells expressing high levels of sialyl Lewis x oligosaccharides PNAS, October 15, 2002; 99(21): 13789 - 13794. [Abstract] [Full Text] [PDF]

				J. Zhang, J. Nakayama, C. Ohyama, M. Suzuki, A. Suzuki, M. Fukuda, and M. N. Fukuda Sialyl Lewis X-dependent Lung Colonization of B16 Melanoma Cells through a Selectin-like Endothelial Receptor Distinct from E- or P-Selectin Cancer Res., August 1, 2002; 62(15): 4194 - 4198. [Abstract] [Full Text] [PDF]

				S.-i. Hakomori The glycosynapse PNAS, January 1, 2002; (2002) 12540899. [Abstract] [Full Text] [PDF]

				T. Jouault, C. Fradin, F. Dzierszinski, M. Borg-Von-Zepelin, S. Tomavo, R. Corman, P.-A. Trinel, J.-P. Kerckaert, and D. Poulain Peptides that mimic Candida albicans-derived {beta}-1,2-linked mannosides Glycobiology, August 1, 2001; 11(8): 693 - 701. [Abstract] [Full Text] [PDF]

				S.-i. Hakomori Inaugural Article: The glycosynapse PNAS, January 8, 2002; 99(1): 225 - 232. [Abstract] [Full Text] [PDF]