Abstract 1: Androgens in glioblastoma: effect of testosterone on the maintenance of glioma stem-like cells

Abstract Glioblastoma is the most common and lethal primary malignant tumor of the central nervous system, with a prevalence 1.6 times more frequent in men than in women, suggesting that sex hormones such as androgens play an important role in tumor progression. Poor prognosis has been associated with the presence of cancer stem cells that in glioblastoma are known as glioma stem cells. There is evidence that patients with glioblastoma have a higher serum concentration of testosterone, as well as a higher expression of the androgen receptor. In addition, the use of androgen receptor antagonists reduces the percentage of cancer stem cells. However, the role of testosterone in regulating stemness is unknown. In this study we analyzed the role of testosterone (100 nM) in processes associated with stem cell maintenance in the human glioblastoma cell lines U251 and T98G. Analyzing the presence of the androgen receptor, a higher expression was found in stem cell-enriched suspension cultures compared to monolayer cultures. The sequences of the stemness-associated genes PROM1, SOX2 and NES presented androgen response elements in their promoter regions. Consistently, testosterone increased the expression of these genes in stem cell-enriched cultures. Additionally, the self-renewal was evaluated by neurosphere generation assays, finding that testosterone favored the generation of primary and secondary neurospheres. Taken together, these results suggest that testosterone regulates the growth of cancer stem cells present in human glioblastoma by promoting the expression of stemness-associated genes as well as their self-renewal. Citation Format: Juan Carlos Quintero-Gallegos, Karina Hernández-Ortega, Martha Robles-Flores, Néstor Fabián Díaz, Ignacio Camacho-Arroyo. Androgens in glioblastoma: effect of testosterone on the maintenance of glioma stem-like cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1.