Fibronectin Network Influences Endothelial Cell Migration During Vascular Morphogenesis in a Breast Cancer Model
Ellis, Kimberly Taylor
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Angiogenesis, the formation of new blood vessels from pre-existing vessels, is a major research topic in the biomedical field due to its role in regenerative medicine, tissue engineering, and cancer development, growth, and metastasis. This process is driven by the demand for oxygen and nutrients from the surrounding tissues, and is heavily regulated by the extracellular matrix (ECM). The ECM is a non-cellular, complex network made up of fibrous proteins, growth factors, and signaling molecules. Many researchers have studied the individual constituents of this protein rich matrix and the specific roles they play during angiogenesis hoping to find a potential target for cancer treatments. Previous research conducted in our lab has established fibroblast and breast cancer cell-derived scaffolds as a platform to investigate tumor angiogenesis. This thesis focuses on the influence of the fibronectin network in the cell-derived scaffolds on endothelial cell (EC) migration. We used pUR4B, a fibronectin polymerization inhibitor, and III-11C, the control peptide that has no effect on fibronectin polymerization to manipulate matrix deposition. We also established a line of green fluorescent protein (GFP) tagged EC’s using lentiviral GFP. After seeding the GFP ECs on the de-cellularized scaffolds, we tracked the migration of the cells and quantified several migration parameters. Our results showed that the polymerized fibronectin restricts EC migration during angiogenesis. Its function to support the surrounding matrix components and adhesive properties are essential for endothelial cell migration. These findings shed new light on the role of polymerized fibronectin in endothelial cell migration during angiogenesis, and further prove its potential as a target for future cancer treatment.