Abstract

In breast cancer, tumor cells collectively move through microenvironments of varying stiffness and fiber structures. Around primary breast tumors, there are gradients of matrix stiffness that mammary epithelial cells (MECs) must navigate for tumor invasion. In addition, the collagen density of the breast tissue becomes more crosslinked and fibrous. Previous studies of breast tumor invasion capture the effect of either soft or stiff environments, not how cells coming from stiff environments behave in softer 3D collagen matrices. Across stiff and soft regions, we have previously shown a mechanical memory-dependent collective migration of epithelial cells on 2D surfaces. In this work, we hypothesize that MECs residing in stiff environments ‘stiff primes’ them for future invasion through softer regions. Furthermore, often these processes occur under hypoxia, and thus it remains unclear how hypoxia priming, and oxygen consumption individually affect invasion. To study these open questions, we develop in vitro and ex vivo models to identify extracellular, subcellular, and intracellular effects caused by mechanical and hypoxia priming.

Committee Chair

Amit Pathak

Degree

Doctor of Philosophy (PhD)

Author's Department

Biomedical Engineering

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

Summer 8-17-2023

Language

English (en)

Download

Share

COinS