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Sialyl Lewis X-dependent Lung Colonization of B16 Melanoma Cells through a Selectin-like Endothelial Receptor Distinct from E- or P-Selectin¹

Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, California 92037 [J. Z., M. S., A. S., M. F., M. N. F.]; The Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan [J. N.]; and Department of Urology, Akita University School of Medicine, Akita 010-8543, Japan [C. O.]

Endothelial carbohydrate binding proteins, E- and P-selectins, are thought to mediate sialylLewis A/X-dependent hematogenous cancer metastasis. We tested this hypothesisusing sialyl Lewis X-dependent B16 melanoma lung targeting andits 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.

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