Stmc-38. eya1 identified by in vitro and in vivo phage display biopanning demonstrates role in glioblastoma stem cell proliferation through oncogene interaction

Glioblastoma stem cells (GSC) comprise of a subpopulation of tumor cells that possess the unique ability to self renew and facilitate tumor growth. Further characterization of these cells will help to understand the unique mechanisms that drive these cells, which will lead to the development of more advanced therapeutic strategies at effectively and specifically targeting these cells. In order to identify novel target proteins that may play a critical role in the maintenance of glioma stem cells, we have employed two separate phage display biopanning strategies to isolate novel 7 amino acid peptides sequences that display preferential binding for GSCs. An in vitro biopanning strategy was employed against GSCs grown in culture, and an in vivo biopanning strategy was performed against intracranially xenografted GSCs. From the peptides that were isolated from each of the two strategies, one peptide sequence combination was found to be isolated in both biopanning strategies. In silico analysis revealed a protein match with Eyes Absent (EYA1) protein, a transcriptional co-activator involved in cell proliferation, as well as DNA damage repair. We demonstrated that EYA1 was preferentially expressed in GSCs and co-localizes with known GSC markers. Inhibition of EYA1 expression through ribonucleic acid interference inhibited GSC formation as evidence by decrease in cell viability, tumorsphere formation, and in vivo tumorigenesis. EYA1 was also found to be present in the tumor vasculat...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: STEM CELLS Source Type: research