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Date of Award
Bachelor of Science
Over the past three decades, more people have been diagnosed with skin cancer than all other cancers combined. Melanoma is the most dangerous form of skin cancer because of its high propensity to metastasize. Several studies have shown that angiogenesis is crucial for the development and progression of the tumors in melanoma. Endothelin 3 (Edn3) is a ligand that binds to Endothelin receptor B (EdnrB), and has been linked to melanoma progression. I developed a highly metastatic mouse model of melanoma dependent on the over-expression of Endothelin 3 (Edn3). I crossed Dct-Grm1 transgenic mice, which aberrantly express metabolic glutamate receptor 1 and develop melanocytic hyperplasia, with K5-Edn3 mice, which conditionally overexpress Edn3 under the Keratin 5 promoter to generate Dct-Grm1/K5-Edn3 mice. Our preliminary data suggest that Edn3 enhances the angiogenic response of the tumors in the Dct Grm1/K5-Edn3 mice compared to controls. The goal of this study is to further investigate the effect of Edn3 in the development of new blood vessels and establish if this process is accompanied by the creation of hypoxic environment in the tumors. In order to visualize the density of blood vessels in the tumors I directly labeled them by cardiac perfusion using a lipophilic carbocyanine dye (DiI). I subsequently removed the tumors and quantified the amount of labeling using confocal microscopy. Diffuse reflectance spectroscopy and a novel spectral interpretation was employed to analyze and compare regions of oxygen saturation in tail tumors of the Dct-Grm1/K5-Edn3 mice and control population. My results indicate that the increased angiogenic response in the presence of Endothelin 3 is accompanied by a significant increase of hypoxic environments. Hindering the expression of Edn3 may serve as a potential starting point to the development of novel therapies to combat this lethal disease.
Valladares, Juan A., "Role of endothelin 3 on the angiogenic response of the tumor in a melanoma mouse model" (2016). Department of Biological Sciences - Undergraduate Honors Theses. 71.
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