title: Effect of the disintegrin eristostatin on melanoma-natural killer cell interactions.
abstract: Malignant melanoma is difficult to treat due to its resistance to chemotherapeutic regimens. Discovery of new pharmaceuticals with inhibitory potential can be helpful in the development of novel treatments. The snake venom disintegrin eristostatin, from the viper Eristicophis macmahoni, caused immunodeficient mice to be significantly protected from development of lung colonization when melanoma cells and the disintegrin were co-injected in vivo into the lateral tail vein compared to vehicle controls. Cytotoxicity assays suggested that eristostatin makes the melanoma cells a better target for lysis by human natural killer cells. Direct binding assays using atomic force microscopy showed eristostatin does specifically bind the surface of the six melanoma cell lines tested. Eristostatin binding was partially inhibited by the addition of soluble RGDS peptide, suggesting an integrin as one likely, but not the sole, binding partner. Studies done with melanoma cells on a culture dish and natural killer cells attached to a cantilever tip in atomic force microscopy showed four major populations of interactions which exhibited altered frequency and unbinding strength in the presence of eristostatin.
authors.affiliation: Department of Medical Laboratory Sciences, University of Delaware, Newark, DE 19716, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hailey
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Adams
authors.forename: Ryan
authors.initials: R
authors.lastname: Penn
authors.forename: Alice
authors.initials: A
authors.lastname: Wong
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: McLane
mesh_terms: D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D002469:Cell Separation; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy*; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D014757:Viper Venoms; C084060:eristostatin; D016650:Fluorescein-5-isothiocyanate