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Bioengineered Submucosa for Studying Effects of Microenvironmental Mechanics on Colorectal Cancer Cells

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The tumor microenvironment is a complex space consisting of a number of stimuli such as: stromal cells, signaling and paracrine factors, as well as extracellular matrix (ECM) components. Each of these factors push and pull cancer cells in different directions and the sum of the interactions defines a cancer cell’s final disposition. Much has been made of the microenvironment in recent years; one hotly researched aspect is ECM mechanics. In terms of the mechanical interaction of the ECM and the cancer cell, a number of observations have been made, such as: stiffer environments produce more aggressive cancer cells and facilitate migration and invasion, and aligned matrices are associated with healthy tissues while unaligned matrices are associated with poor prognosis. Although there is a wealth of literature describing both stiffness and alignment in vivo, there are few studies that determine the extent of these factors in vitro. In this study, we produce submucosal organoids with varying matrix alignment and embed an HCT-116, colon carcinoma cell line, spheroid into our organoids to simulate an integrated tumor compartment. Through the modulation of our submucosal model, we determine the effects of varying alignment and stiffness on colorectal cancer cell phenotype. After identifying a possible pathway, from matrix mechanics transduction to oncogenic transcription, we modulate the cancer cells in a manner to induce or reduce chemosusceptibility to 5-fluoruracil.
Collagen mechanics
Extracellular matrix
Organ models
Devarasetty, Mahesh (author)
Soker, Shay (committee chair)
Skardal, Aleksander (committee member)
Almeida-Porada, Graca (committee member)
Verbridge, Scott (committee member)
Hall, Adam (committee member)
2017-06-15T08:35:35Z (accessioned)
2017-06-15T08:35:35Z (available)
2017 (issued)
Biomedical Engineering (discipline)
http://hdl.handle.net/10339/82174 (uri)
en (iso)
Wake Forest University
Bioengineered Submucosa for Studying Effects of Microenvironmental Mechanics on Colorectal Cancer Cells

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