Profiling the Effects of Extracellular Matrix Composition on Engineered Microvessel Permeability
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Abstract
Blood vessels in tumors are often very permeable or leaky. This characteristic of tumor blood vessels enhances the routes for vascular intravasation of cancer cells during metastasis while also disrupting the delivery of therapeutics. The tumor extracellular matrix (ECM) has increased concentrations of fibrillar collagen and the glycosaminoglycan (GAG) hyaluronic acid (HA), which also results in increased mechanical stiffness. Tumor matrix stiffening promotes cancer cell migration and blood vessel permeability. Here I present findings that build off my prior experience with stiffness measurements of ECM hydrogels and microvessel engineering. My presentation will include the modeling of tumor blood vessels using engineered microvessels in vitro that are surrounded by an ECM of known composition and stiffness. The focus of these studies is to construct a model that profiles the effects of ECM composition has on physical properties of blood vessels and its vasculature. Future investigations will utilize the comprehensive model to compare and analyze the vascular responses to non-contact induced electric fields (iEFs) treatment, which our group previously showed significantly suppress the migration of metastatic breast cancer cells. Collectively, this research will make fundamental advances in our understanding of the interaction between ECM composition and the physical properties and vasculature of blood vessels.