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Author ORCID Identifier

https://orcid.org/0000-0001-7542-4105

AccessType

Open Access Dissertation

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2022

Month Degree Awarded

May

First Advisor

Shelly R. Peyton

Second Advisor

Kathleen Arcaro

Third Advisor

Leonid Pobezinsky

Fourth Advisor

Yubing Sun

Subject Categories

Biomaterials | Cancer Biology

Abstract

Accumulation of epigenetic and genetic changes results in oncogenic transformation of epithelial cells. During breast cancer metastasis, while the extracellular matrix (ECM) becomes stiffer, breast cancer cells transmit mechanical forces into intracellular tension and activate signaling pathways influencing growth, migration, and metastasis. Once cancer cells detach from the primary tumor, they intravasate into the vasculature, survive in the circulation, extravasate and adapt to a new microenvironment of a secondary site. Throughout the process, only a very small population of cancer cells survive, and they are likely to reside at the metastatic sites for several years. The most frequent metastatic sites for breast cancer are brain, lung, liver, and bone. Each has distinct mechanical and biochemical properties. To recapitulate this selection process, we grew triple negative breast cancer (TNBC) on soft and stiff biomaterials in addition to the widely used cell culture platform, tissue culture polystyrene over time. Alterations in phenotypes and gene expressions were captured. Since TNBC is heterogeneous, we were interested in investigating the phenotypes of their subclonal compositions. By isolating subclones from the established TNBC cell lines, we were able to measure variations in growth, motility, response to ECM stiffness and proteins, and drug response, etc.

DOI

https://doi.org/10.7275/28638785

Available for download on Saturday, May 13, 2023

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