3D Culture Models to Monitor Tumor Angiogenesis

Professor: Claudia Fischbach-Teschl

Project Description: Glioblastoma Multiforme, the most malignant type ofbrain tumor, is characterized by extensive invasion and vascularization. Consequently, vascular development in this and many types of cancers has been the focus of many clinical and research approaches in understanding the tumor microenvironment and the role vasculature has in reshaping and promoting disease progression. Blood vessel growth in diseased tissues often appears tortuous and incoherent, being a consequence of biochemical and environmental dysregulation in the cell microenvironment. Specifically, the extracellular matrix (ECM) and its topological, mechanical, and biochemical properties are critical in understanding the relationship between cell behavior and disease progression. Indeed, while blood vessels support glioma cells, these tumor cells appear to have a regulatory and contributory effect on the tumor vasculature and endothelial cells. To assess this, our lab has developed models that involve hydrogels consisting of several different matrix proteins in order to mimic the tissue ECM. Following this, assessment and live characterization of angiogenesis and matrix remodeling are critical in understanding blood vessel growth and the different conditions under which it would be altered. Time-lapse confocal imaging combined with hydrogel incubation and culture would be the crux of analyzing specific endothelial cell behaviors and matrix properties. By participating in this project, a student researcher would be exposed to the fabrication of our hydrogels, basic cell culture and assays, imaging analysis, and quantification of cell behavior. The results from these experiments will provide valuable information for our understanding of how endothelial cells remodel their environment and the role of stimulus in endothelial cell behavior.