Date of Award

5-31-2018

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Physics, Applied

First Advisor

Jonathan Celli

Second Advisor

Chandra Yelleswarapu

Third Advisor

Stephen Arnason

Abstract

Cancer is a complex and lethal disease, whose behavior is determined by biological, chemical, and physical cues from its environment. Pancreatic cancer, notoriously difficult to detect until later stages, produces poor prognosis statistics, and very invasive, shall be used in this thesis to investigate the prominent desmoplastic relationship between cancer and the extra cellular matrix (ECM) microenvironment in which it inhabits. In this study the ECM was used as a model system to explore how the microenvironment's rigidity impacts growth behavior and initial phases in invasive progression.

In this thesis I characterize the microenvironment, where three-dimensional pancreatic tumor models shall be embedded to uncover the relationship between tumor and the physical microenvironment it inhabits by measuring the rigidity and adhesive qualities of the microenvironment. If small enough changes, limited by the techniques used in this study, are made to the microenvironment's rigidity is capable of severely limiting the invasive behavior of the tumor models, it can be asserted that there exists a delicate relationship between the microenvironment's physical properties and growth behavior.

This study time-lapse microscopy was utilized to observe tumor invasion and growth in a variety of commercial basement membranes whose rigidity has been manipulated to modify rheological characteristics independently of biological composition. Embedding tumor spheroids on rigidity-tuned extracellular matrices will provide insight on cancer cells' interactions with its environment. Matrix rigidity tuning will be accomplished by adding and tweaking concentration of agarose in a naturally derived basement membrane, with the expectation of finding a correlation between matrix stiffness and tumor morphogenesis. This study aims to illustrate the impact of ECM stiffness on cancer cells through rheology analysis.

Comments

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caide_supplementary_1.wmv (4458 kB)
Spheroid growth over 72 hours in a 1.0% Agarose ECM

caide_supplementary_2.wmv (4677 kB)
Spheroid growth over 72 hours in a 0.125% Agarose ECM

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