Date on Senior Honors Thesis
5-2024
Document Type
Senior Honors Thesis
Department
Anatomical Sciences and Neurobiology
Author's Keywords
Tumor Invasion; Glioblastoma; Mesenchymal transitions; Brain tumors
Abstract
Glioblastoma (GBM), a highly aggressive primary brain tumor originating in glial cells, poses a significant challenge due to its rapid growth and invasive nature within healthy brain tissue.
Current treatments involve surgical resection, chemotherapy, and radiation. These treatments alone are not enough to cure this disease, and a better understanding the mechanics of the tumor micro-environment is imperative to furthering the field of cancer research. This research focuses on understanding the tumor microenvironment's impact, specifically investigating the role of stromal cell-derived factor 1 (SDF-1) mechanics on GBM aggressiveness. SDF-1 is known to facilitate disease progression by facilitating chemotaxis toward the sub-ventricular zone (SVZ). GBM cells reaching this area of the brain represents a major event that when prevented stands to significantly increase the survival of the patient. The presence of SDF-1 together confer GBM cells the ability to transition into a mesenchymal state. This pro-neural to mesenchymal transition (PMT) is known to be a marker of a more aggressive tumor phenotype. Preliminary experiments explore SDF-1 effects on gene expression over five days, utilizing western blot quantification. The overall project has elucidated mechanisms driving GBM's invasive behavior, showing that gene products such as ZEB-1, which are known to facilitate PMT, are unregulated in the presence of SDF-1. These preliminary and future experiments have provided valuable insights for developing targeted therapeutic strategies.
Recommended Citation
Froman-Glover, Charles T., "SDF-1α mediates primary tumor escape in glioblastoma through activation of mesenchymal transitions." (2024). College of Arts & Sciences Senior Honors Theses. Paper 321.
Retrieved from https://ir.library.louisville.edu/honors/321
Lay Summary
We all know basically that cancer is when a cell or group of cells from our body “go rogue” and start messing things up. Something that is less talked about is how these rogue cells have a robust toolbox full of everything they would ever need to make their host the most hospitable place to live. In this way cancer is less of a rogue, and more of an alien invader come to conquer earth, but learned how to drive every type of car, fly every type of plane, look like every type of person, and speak every language on earth. The garden variety cancer type is like this. Glioblastoma is worse. Glioblastoma is unique in that it only grows and exists in the brain and arises when a brain support cell goes rogue.
The problem with this tumor type is that because it grew and developed in the brain when it was a “good guy” it remembers how to walk and run in that environment and glioblastoma will not sit still. Its ability to move is tied to its very identity. There is a chemical in the brain that acts sort of like a cattle dog. It keeps the cows—in this analogy stem cells—in the corral. The thing is glioblastoma cells are pretty good at sniffing that chemical out and extending out to meet the cows in that corral. Glioblastoma can secrete chemicals from its vast tool kit--that sticks around as a painful reminder that it used to be a productive member of the brain’s society—to turn the cows against the farm—or brain so to speak. In glioblastoma this marks what many physicians and scientists woefully regard as the point of no return.
The purpose of this study is to determine what the “cattle dog” chemical is doing to the glioblastoma cells, and what qualities it as affording that cold hand of glioblastoma that allows it to find its way far from the primary source of glioblastoma.
