Effects of Small-Molecule Inhibitors of FGFR, Integrins, and FAK on L1CAM-Stimulated Glioblastoma Stem Cell Motility and Proliferation


  • Emily Borell, Biological Sciences, University of Delaware

Faculty Mentor(s)

  • Deni Galileo, Biological Sciences, University of Delaware


Glioblastoma (GBM) is an aggressive, deadly, and incurable form of brain cancer. The current prognosis for patients diagnosed is just over a year, as no current long-term treatments exist. Glioblastoma is difficult to treat due to the fact that glioblastoma stem cells (GSCs) rapidly invade the surrounding brain tissue and are resistant to radiation and chemotherapy. These GSCs also make tumor removal difficult because even after the tumor is surgically removed, it often regrows due to the proliferation of GSCs that were not removed during surgery. The Galileo Lab previously has found evidence to support that the L1CAM cell adhesion protein stimulates the motility and proliferation of GBM cells and acts through the integrin, focal adhesion kinase (FAK), and fibroblast growth factor receptor (FGFR) signaling pathways. Additionally, decreased motility and proliferation of GBM cells from established glioblastoma cell lines was observed in previous experiments when using the following inhibitors: FGFR inhibitor PD173074, the FAK inhibitors PF431396 and Y15, and the αvβ3/αvβ5 integrin inhibitor cilengitide. Those results were extended by using these inhibitors to study the effects on several lines of GSCs. The GSCs were exposed to each of the four inhibitors, then a cell motility “super scratch” assay was performed to measure the velocity of migrating cells using time-lapse microscopy. Following the time-lapse experiment, a proliferation assay was performed on the same treated cells. This was conducted by staining the DNA in the cells before analyzing the samples using flow cytometry to determine the percentage of the cells in the S phase of the cell cycle. Analysis of treated cells revealed they had decreased velocity compared to untreated, positive control cells. This suggests that these inhibitors have the potential to reduce the aggressiveness of GSCs by decreasing the invasion in GBM tumors.  Cell cycle analyses are ongoing.