title: Targeting selectins and selectin ligands in inflammation and cancer.
abstract: Inflammation and cancer metastasis are associated with extravasation of leukocytes or tumor cells from blood into tissue. Such movement is believed to follow a coordinated and sequential molecular cascade initiated, in part, by the three members of the selectin family of carbohydrate-binding proteins: E-selectin (CD62E), L-selectin (CD62L) and P-selectin (CD62P). E-selectin is particularly noteworthy in disease by virtue of its expression on activated endothelium and on bone-skin microvascular linings and for its role in cell rolling, cell signaling and chemotaxis. E-selectin, along with L- or P-selectin, mediates cell tethering and rolling interactions through the recognition of sialo-fucosylated Lewis carbohydrates expressed on structurally diverse protein-lipid ligands on circulating leukocytes or tumor cells. Major advances in understanding the role of E-selectin in inflammation and cancer have been advanced by experiments assaying E-selectin-mediated rolling of leukocytes and tumor cells under hydrodynamic shear flow, by clinical models of E-selectin-dependent inflammation, by mice deficient in E-selectin and by mice deficient in glycosyltransferases that regulate the binding activity of E-selectin ligands. Here, the authors elaborate on how E-selectin and its ligands may facilitate leukocyte or tumor cell recruitment in inflammatory and metastatic settings. Antagonists that target cellular interactions with E-selectin and other members of the selectin family, including neutralizing monoclonal antibodies, competitive ligand inhibitors or metabolic carbohydrate mimetics, exemplify a growing arsenal of potentially effective therapeutics in controlling inflammation and the metastatic behavior of cancer.
authors.affiliation: Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine, Room 669, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Barthel
authors.forename: Jacyln D
authors.initials: JD
authors.lastname: Gavino
authors.forename: Leyla
authors.initials: L
authors.lastname: Descheny
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Dimitroff
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002465:Cell Movement; D016503:Drug Delivery Systems; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008024:Ligands; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D019087:Selectins / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D008024:Ligands; D019087:Selectins