Researcher(s)
- Marian Wehner, Biological Sciences, University of Delaware
Faculty Mentor(s)
- Deni Galileo, Department of Biological Sciences, University of Delaware
Abstract
Glioblastoma (GBM) is the most common and aggressive form of brain cancer. Glioblastoma stem cells (GSCs) are thought to be the primary cause of growth of the initial tumor, despite only making up about 1% of the total tumor cells, and of tumor regrowth after they invade the surrounding brain tissue to escape surgical resection. Further understanding of GSCs and how they relate to “differentiated” (non-stem) GBM cells is essential to understanding how GBM grows and spreads within the brain. I tested the hypothesis that GSCs are a cell “state” (vs. a stable cell phenotype) that can be induced by specific cell culture conditions. To approach this, several long-established non-GSC GBM cell lines were grown in both their normal high-serum (differentiation) media and in stem-cell media, followed by analysis of expression for several GSC marker proteins. After a week or more in the different media, cells were fixed and fluorescently stained for nestin, sox-2, integrin α6, and L1CAM and analyzed by flow cytometry. The data was analyzed to determine if the percentage of cells expressing the proteins differed depending on the type of, and length of time in, the different media. Results varied widely between different GBM cell lines. U-87 MG and U-118 MG cells detached from the culture dishes in stem cell media and were not further analyzed. T98G cells showed an increase in the percentage of all GSC markers after seven and twenty days in stem cell media. U-373 MG cells showed different changes depending on their time in stem cell media. Patient-derived GSCs that were previously grown in differentiation media and then grown again in stem-cell media were also analyzed for marker expression. In vivo injection experiments also were begun to determine if the growth and invasive abilities differed between cells grown in the different media. It is concluded that expression of GSC “marker” proteins can be modulated by growing GBM cells in stem cell media. Functional consequences of the marker expression changes have yet to be determined.