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Date of Award

Spring 4-15-2019

Degree Type

Thesis

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Lidia Kos

Second Advisor

Walter Goldberg

Abstract

Melanoma is a cancer that is caused when pigment producing cells called melanocytes acquire cellular damage and begin to proliferate. Some major factors that affect melanoma progression include environmental carcinogens and genetic mutations. The tumor microenvironment is a rising field of interest in studying aggression in many cancers. A specific signaling pathway between endothelin 3 (Edn3) and endothelin receptor b (Ednrb) has been used as a marker for aggressive types of melanoma, but the role that Edn3 plays in tumor progression has not been addressed. This thesis studied the effects of Edn3 in mice with melanoma by using a model that overexpresses Edn3 through the Keratin 5 promoter and is thus referred to as a K5-Edn3mouse. TenK5-Edn3and ten wild-type mice lacking the transgene were both injected with 106B16F10-GFP. Primary tumors were measured biweekly for a full month. A second round of injection was done with 105YUMM1.7-GFP cells, which carry three key driver mutations found in human melanomas. These tumors were grown and measured for 21 days. Flow cytometric analysis was done on the YUMM1.7-GFP tumors to check for Ednrb expression in the tumor microenvironment. In both cell lines, K5-Edn3mice grew statistically larger tumors at faster rates than the wild-type. Metastatic tissue was found only in the lungs of the K5-Edn3 mice. Flow cytometric analysis showed that a subpopulation of tumorigenic cells and stromal cells express Ednrb in both mice groups. Together, the results indicate that overexpressing Edn3 promotes melanoma growth and increases the metastatic potential of primary tumors. Furthermore, Ednrb expression found in tumorigenic and stromal cells in the microenvironment may be contributing to the overall tumor progression in melanoma. Future directions should further characterize the stromal cell subpopulations expressing Endrb, which may give rise to novel therapies that inhibit their downstream effectors.

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