DOI
https://doi.org/10.25772/BWSP-M376
Defense Date
2023
Document Type
Thesis
Degree Name
Master of Science
Department
Biomedical Engineering
First Advisor
Christopher Lemmon
Second Advisor
Rebecca Heise
Third Advisor
Patricia Sime
Abstract
Breast cancer is the second leading cause of death in women, second to lung cancer. It’s one of the most well-known cancers, with almost 300,000 new cases estimated to be diagnosed in 2023. Breast cancer often begins in ductal epithelial cells, and these cells will typically undergo a cellular transformation process known as epithelial-mesenchymal transition (EMT) in early stages. Breast cancer becomes deadly when it reaches a metastatic stage. As a part of the metastatic process, transformed cells will conduct remodeling of the extracellular matrix (ECM) to allow for migration of an otherwise non-migratory cell type.
As dense tumors form, regions of low oxygen, or hypoxia, will begin to develop. In hypoxia, cells will undergo anaerobic respiration, creating lactic acid as a byproduct. Buildup of lactic acid in the environment leads to a decrease in extracellular pH. The lack of oxygen and decrease of extracellular pH facilitate cellular transformation, further encouraging cellular migration.
This work aims to better understand the role of changes in extracellular pH and low oxygen environments on EMT, and to further investigate the role of TGF-β1 signaling and fibronectin assembly on cellular transformation in low O2. We cultured cells in acidic environments in normoxia to investigate the role pH may play in hypoxia induced EMT. Cells were also cultured in hypoxia and treated with FUD or TGFB1 gene knockout, and we found that inhibition of TGF-β1 signaling or FN assembly can mitigate EMT in hypoxia. This work could provide insight into preventative treatment against cellular transformation.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
9-26-2023