Date of Graduation

5-2017

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Rajaram, Narasimhan

Committee Member/Reader

Jensen, Morten

Committee Member/Second Reader

Wolchok, Jeff

Abstract

Breast cancer metastasis is the main cause for mortality in breast cancer patients. However, knowledge of metastatic recurrence is limited, and there is a need to understand metastatic recurrence in order to treat breast cancer patients more effectively. Highly invasive metastatic breast cancer has shown to exhibit metabolic adaptability, transitioning from glycolysis to oxidative phosphorylation in the presence of microenvironmental stress. NADH and FAD are naturally occurring cofactor products during glycolysis and oxidative phosphorylation, respectively, and they are of particular importance during these metabolic processes due to their endogenous fluorescence. Measuring the ratio of fluorescence intensities of these cofactors through a redox ratio allows for the quantification of the comparative levels of glycolysis and oxidative phosphorylation occurring in breast cancer cells. Two-photon imaging was used to assess the redox ratio of 4T1KOT, a variant of highly metastatic 4T1 cells with deletion of the TWIST gene, a gene known to promote metastasis. This thesis reports that 4T1KOT cells, compared to metastatic 4T1 cells, have a decreased redox ratio at normoxia conditions, and they also lose their metabolic adaptability under hypoxia-reoxygenation stress. This study demonstrates that metabolic adaptability to hypoxia-reoxygenation stress could be used as a biomarker for breast cancer metastatic potential.

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