University of Louisville
SDF-1 Promotes Mesenchymal Transitions and Invasiveness in Glioblastoma
Grade Level at Time of Presentation
Senior
Major
Neuroscience
Institution 23-24
University of Louisville
KY House District #
37
KY Senate District #
10
Faculty Advisor/ Mentor
Dr. Joseph Chen, PhD.
Department
Dept. of Bioengineering
Abstract
Glioblastoma (GBM), a highly aggressive primary brain tumor originating in glial cells, poses a significant challenge due to its rapid growth and invasion into healthy brain tissue.
Current treatments involve surgical resection, chemotherapy, and radiation; however, these approaches have been ineffective due in part to the rapid infiltration of GBM cells. Recent reports have revealed that this rapid infiltration occurs asymmetrically with routes of invasion that appear to be migrating toward the subventricular zone (SVZ) within the brain. Notably, once the tumor cells reach the SVZ, patient prognosis plummets. Investigating this axis is critical for the development of novel therapeutic approaches to limit invasion and improve prognosis. Within the SVZ, a known chemokine, stromal derived growth factor (SDF-1), is released and is thought to be a main driver of drawing GBM cells out of the tumor. However, the role of SDF-1 as a chemokine is insufficient to describe the cell’s ability to traverse the significant mechanical and microenvironmental barriers present in the brain. Recent work in our lab suggest that a phenotypic transition of cells called proneural to mesenchymal transition is needed to efficiently migrate through the dense parenchyma. Thus, in this work, we test the hypothesis that SDF-1 plays both a chemokinetic and a pro-mesenchymal role in facilitating GBM cell escape and successful migration to the SVZ. Our investigation employs patient derived GBM cells and bioengineering tools such as hydrogels mimicking brain tumor stiffness. Preliminary experiments reveal that SDF-1 stimulation over five days elevated mesenchymal protein expression, ZEB1, and CD44 and enhanced migration capacity in a 2D context. These data provide evidence that SDF-1 may be a master regulator of GBM phenotype and invasiveness, highlighting its utility for pharmacological targeting.
SDF-1 Promotes Mesenchymal Transitions and Invasiveness in Glioblastoma
Glioblastoma (GBM), a highly aggressive primary brain tumor originating in glial cells, poses a significant challenge due to its rapid growth and invasion into healthy brain tissue.
Current treatments involve surgical resection, chemotherapy, and radiation; however, these approaches have been ineffective due in part to the rapid infiltration of GBM cells. Recent reports have revealed that this rapid infiltration occurs asymmetrically with routes of invasion that appear to be migrating toward the subventricular zone (SVZ) within the brain. Notably, once the tumor cells reach the SVZ, patient prognosis plummets. Investigating this axis is critical for the development of novel therapeutic approaches to limit invasion and improve prognosis. Within the SVZ, a known chemokine, stromal derived growth factor (SDF-1), is released and is thought to be a main driver of drawing GBM cells out of the tumor. However, the role of SDF-1 as a chemokine is insufficient to describe the cell’s ability to traverse the significant mechanical and microenvironmental barriers present in the brain. Recent work in our lab suggest that a phenotypic transition of cells called proneural to mesenchymal transition is needed to efficiently migrate through the dense parenchyma. Thus, in this work, we test the hypothesis that SDF-1 plays both a chemokinetic and a pro-mesenchymal role in facilitating GBM cell escape and successful migration to the SVZ. Our investigation employs patient derived GBM cells and bioengineering tools such as hydrogels mimicking brain tumor stiffness. Preliminary experiments reveal that SDF-1 stimulation over five days elevated mesenchymal protein expression, ZEB1, and CD44 and enhanced migration capacity in a 2D context. These data provide evidence that SDF-1 may be a master regulator of GBM phenotype and invasiveness, highlighting its utility for pharmacological targeting.