Semester of Graduation

Fall 2019

Degree

Master of Science in Biological and Agricultural Engineering (MSBAE)

Department

Department of Biological and Agricultural Engineering

Document Type

Thesis

Abstract

Tumors derived from breast tissue possess the ability to manipulate and permanently alter their surrounding tissue. Studies demonstrate that tissues surrounding breast tumors have differences in secreted factors as well as extracellular matrix (ECM) deposition and structure. However, some fundamental gaps exist within this paradigm: specifically, what exacerbates this transformation and are these changes maintained between the subtypes of breast tumors? Therefore, a targeted evaluation of the effects of the tumor on the stromal microenvironment in a subtype specific manner will be invaluable. To determine if tumor aggressiveness and subtype differentially regulate the tumor microenvironment, a model must be constructed that allows for the evaluation of tumor molecular and physical composition. Here we set forth to optimize a method of tumor decellularization and employ this method to evaluate structural and molecular changes within the tumor. Secondly, we sought to identify the source of tumor remodeling through the use of cancer conditioned media-based experiments. Our results demonstrate that tumors can be decellularized, maintain matrix structure and composition, and be used as scaffolds for cellular reseeding. Furthermore, we were able to identify human adipose derived stem cells (hASCs) as a source for tumor microenvironment remodeling in triple negative breast cancer (TNBC). Specifically, by maintaining a pro-inflammatory phenotype matching their role in early-wound healing. The stromal remodeling demonstrated in this paper has elucidated a potential mechanism of tumor progression that is unique between breast tumor subtypes. These effects leave lasting impacts on the microenvironment of tissue surrounding breast tumors and likely play a role in breast cancer recurrence. Due to this, it is of use to continue identifying these changes in an effort to clarify the dynamic and reciprocal nature of both the cancer-stroma interaction and matrix.

Committee Chair

Martin, Elizabeth

Available for download on Thursday, October 29, 2020

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