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Targeting selectins and selectin ligands in inflammation and cancer Barthel SR; Gavino JD; Descheny L; Dimitroff CJExpert Opin Ther Targets 2007[Nov]; 11 (11): 1473-91Inflammation 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.|*Drug Delivery Systems[MESH]|Animals[MESH]|Anti-Inflammatory Agents/administration & dosage[MESH]|Antineoplastic Agents/administration & dosage[MESH]|Cell Movement[MESH]|Humans[MESH]|Inflammation/*drug therapy/physiopathology[MESH]|Ligands[MESH]|Neoplasm Metastasis/drug therapy[MESH]|Neoplasms/*drug therapy/physiopathology[MESH]|Selectins/drug effects/*metabolism[MESH] |
