Abstract
Abstract The tumor microenvironment is complex and heterogeneous, comprised of the extracellular matrix, various cell types, blood vessels, and soluble factors. Multiple interactions occur between tumor cells and their environment which affect cellular behavior and the composition of the tumor microenvironment. Changes to the composition of collagen within the tumor microenvironment have been linked to an increased risk of developing breast carcinoma and an increased invasiveness of breast cancer cells. The goal of this study is to understand how selected, well-controlled manipulations of the collagen composition alter the behavior of an invasive human breast cancer cell line, MDA-MB-231. A BioMEMS device will be loaded with molecules that alter collagen and inserted into a 3-D 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 collagen, increased collagen crosslinking and inhibition of a collagen cross-linker produced by tumor cells. Confocal reflectance microscopy, atomic force microscopy, and environmental scanning electron microscopy are utilized to characterize the changes induced and the rates at which the changes occur. Changes in gene expression are investigated to determine the pathways each of the collagen manipulations induce which result in the observed changes to cellular behavior. The observed alterations in cellular phenotype resulting from these collagen changes will help to better understand what degree of changes occur within breast carcinoma resulting in cancer progression. Citation Format: Ashley N. Clark, James Williams, Michael Padgen, Patricia Keely, James Castracane. Study of the effects of localized collagen manipulation on the behavior of breast cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A082.
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