Date of Award

2016

Document Type

Open Access Dissertation

Department

Biomedical Science

Sub-Department

School of Medicine

First Advisor

E. Angela Murphy

Second Advisor

Mitzi Nagarkatti

Abstract

More than two-thirds of the adult population in the United States is classified as overweight or obese. In order to fully comprehend this rapidly increasing dilemma, further understanding of the complex phenomena that are involved with obesity and its many comorbidities is necessary. Chronic inflammation represents a distinctive, recurrent feature of obesity and has been associated with an increased risk of breast cancer. Monocyte chemoattractant protein 1 is a crucial component of the inflammatory process and represents a potential therapeutic treatment target, not only in obesity but also in breast cancer. Using a monocyte chemoattractant protein deficient model, we examined the role of this chemokine in the obesogenic inflammatory environment and results indicate that it can play a protective role in the development of adiposity and metabolic perturbations in a high fat diet-induced obesity murine model. Additionally, we examined the role of this chemokine in a model of triple negative breast cancer and report that deletion significantly reduces tumorigenesis and localized inflammation. Finally, we tested the central hypothesis that chronic inflammation plays a critical role in the progression and severity of obesity-induced hormone-dependent breast cancer and report significant proneoplastic effects. Further understanding of the etiopathogenesis of obesity and breast cancer has profound, prognostic effects. Therefore, continued research is required so that novel targeted therapies can be developed in this ever increasing portion of the population.

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