The effect of eristostatin on melanoma-natural killer cell interactions
| Author(s) | Hailey, Stefan | |
| Date Accessioned | 2012-07-11T12:03:01Z | |
| Date Available | 2012-07-11T12:03:01Z | |
| Publication Date | 2011 | |
| 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 purified snake venom disintegrin eristostatin, from the viper Eristocophis macmahoni, caused immunodeficient mice to be significantly protected (47-57%, p<0.003) 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, while previous investigators have demonstrated that melanoma cells may alter NKG2D ligand expression in order to escape natural killer cell targeting. Direct binding assays using atomic force microscopy show eristostatin does bind the surface of the six melanoma cell lines tested and this interaction is specific. Eristostatin binding was partially inhibited by the addition of 0.2 mM soluble RGDS peptide suggesting an integrin as one likely, but not the sole, binding partner. Studies were done with melanoma cells on a culture dish and natural killer cells attached to the AFM cantilever tip, in the presence and absence of 0.5 μM eristostatin. There were four major populations of interactions which, interestingly, showed altered frequency and unbinding strength in the presence of eristostatin. Surface expression assays showed that eristostatin did not cause a change in the surface expression of the NKG2D ligand, MICA/B. | en_US |
| Advisor | McLane, Mary Ann | |
| Degree | M.S. | |
| Department | University of Delaware, Department of Biological Sciences | |
| URL | http://udspace.udel.edu/handle/19716/11183 | |
| Publisher | University of Delaware | en_US |
| dc.subject.lcsh | Killer cells. | |
| dc.subject.lcsh | Melanoma. | |
| dc.subject.lcsh | Eristostatine. | |
| Title | The effect of eristostatin on melanoma-natural killer cell interactions | en_US |
| Type | Thesis | en_US |