Date of Award
Biomedical Sciences (M.H.S.)
Glioblastoma multiforme (GBM) is the most common primary brain tumor in humans and is characterized as being highly aggressive and invasive, with the ability to locally invade different areas of the central nervous system (CNS). GBM local invasion undergoes an epithelial to mesenchmal like (EMT) process characterized by the loss of cell-cell adhesion and increased cell mobility. The EMT-like switch in GBM is triggered by a single transcription factor, Twist1, and is characterized by the loss of cell clustering, re-organization of the basement membrane, and increased cell migration. GBM invasion depends on the remodeling of the extracellular matrix (ECM) microenvironment, which is induced in part by activated matrix metalloproteinases (MMPs). MMPs have proteolytic activity, acting in the breakdown of the basement membrane (BM), and facilitating cell proliferation, adhesion, migration and angiogenesis. The progression of GBM tumor malignancy is a multistep process that involves cell-cell and cell-ECM adhesion, invasion and migration. In this study, we examined the ability of the neural ECM proteins vitronectin, fibronectin, laminin and collagen IV to trigger an EMT-like response in GBM. We found that, monolayer formation of GBM cells on purified ECM proteins exhibited the mesenchymal phenotype, but this did not lead to the induction of the transcription factor Twist1, a marker used to determine GBM invasion. On the contrary, we found that GBM cells grown on collagen IV show heightened levels of Twist without the EMT-like switch in morphologies. These findings suggest an important role for collagen IV in the process of GBM local invasion.
Orey, Stephen C., "The Role of Extracellular Matrix Proteins on Epithelial to Mesenchymal Transition in Glioblastoma Multiforme" (2013). Masters Theses. Paper 62.