Date of Award

2021

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering (PhD)

Administrative Home Department

Department of Biomedical Engineering

Advisor 1

Smitha Rao

Advisor 2

Marina Tanasova

Committee Member 1

Megan Frost

Committee Member 2

Sang Yoon Han

Committee Member 3

Rupali Datta

Abstract

As of January 2018, there are 3.1 million women diagnosed of breast cancer. The 5-year survival rate for non-invasive breast cancer is 99%, which drastically reduces to 22% if the caner metastasizes. Recent efforts in cancer research have highlighted the significance of diet and nutrient uptake. While the dependence of cancer on fructose has been reported [7, 8], the impact of this unique adaptation on the proliferation and migration of cancer leading to metastasis has not been studied. Here, we target the nutrient requirement of cancer cells using transporter-specific fructose mimics in a microfluidic platform to distinguish behavior of cancer cells. The impact of uptake of fructose, expression of fructose-specific transporter GLUT5 (Chapter 2) and changes in cell migration behavior in the presence of different nutrient conditions (Chapter 3) were quantitatively assessed. Approaches to determine expression of GLUT5 in 3D constructs using nanofiber scaffolds were explored (Chapter 4). Thus, this research aims at developing a methodology to distinguish fructose uptake through GLUT5 in malignant and non-malignant breast cancer cells and compare the responses driven by the preferential uptake of fructose and fructose mimics. The microfluidic device and the 3D scaffold together will enable testing, characterizing, and quantifying the specific response to fructose mimics and allow real time monitoring and in-situ characterization. Understanding cancer cell adaptation(s) due to sugar uptake has the potential to improve our understanding of nutritional contributions towards cancer growth and impact diagnosis, prevention, treatment, and rehabilitation from cancer.

Available for download on Tuesday, August 09, 2022

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