Date of Award

1-1-2013

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Nanoscale Science and Engineering

Program

Nanoscale Sciences

Content Description

1 online resource (v, 43 pages) : illustrations (some color)

Dissertation/Thesis Chair

James Castracane

Committee Members

Nathaniel Cady, Yubing Xie, Patricia Keely, Nadine Hempel

Keywords

BIOMEMS, Extracellular Matrix, Tumor Microenvironment, Metastasis, BioMEMS, Collagen, Extracellular matrix proteins, Biomedical materials

Subject Categories

Biology | Nanoscience and Nanotechnology

Abstract

Approximately 90% of all cancer related deaths can be attributed to the occurrence of metastasis. There are multiple changes that occur within the tumor microenvironment that have been correlated with the onset of metastasis. Different cell types, extracellular matrices, blood vessels, and soluble factors are some of the various components that make up the complex, heterogeneous microenvironment that exists within a tumor. The dynamic relationship between tumor cells and their surrounding environment makes it an ideal environment to study triggers of metastasis, such as the modification of the extracellular matrix. Changes in the multiple aspects of extracellular matrix composition have been linked to an increased risk of developing breast carcinoma and increased invasiveness of breast cancer cells. The influence of the environmental composition and structure on cellular behavior causes the affected tumor cells to further modify the composition and structure of the extracellular matrix in which they are embedded. The Nano Intravital Device (NANIVID) is a versatile, biocompatible device that allows for the manipulation of the tumor microenvironment in vitro and in vivo, providing a platform to study various aspects of tumor progression. The goal of this study is to validate the NANIVID as a platform to produce selected, well-controlled manipulations of 3D collagen gel composition. The NANIVID will be loaded with molecules that affect collagen composition and then inserted into a 3-D collagen gel containing MDA-MB-231 cells to establish a localized gradient of these molecules. The compositional changes include increased collagen concentration through stimulating cellular deposition of extracellular matrix proteins using l-ascorbic acid, increased collagen crosslinking using lysyl oxidase, and inhibition of a collagen cross-linker produced by tumor cells using beta-aminopropionitrile. Confocal reflectance microscopy, immunofluorescence confocal microscopy, and fluorescence spectroscopy are utilized to observe the changes in collagen induced by the gradient of ECM modifying molecules produced by the NANIVID. The validation of the NANIVID as a platform to modify the tumor extracellular matrix will allow a way to observe changes to cellular behavior in these modified environments and the amount of modification that must take place to induce a more invasive phenotype leading to metastatic disease.

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