Abstract 2448: Galectin-3 regulates stemness and cellular states in glioblastoma stem cells

Abstract

Abstract Glioblastoma stem cells (GSCs) are a subset of cells in the Glioblastoma (GBM) tumor microenvironment that play an important role in tumor heterogeneity, aggressiveness, recurrence, and therapy resistance. Dynamic environmental, transcriptional, and epigenetic oscillations envelope GSCs in a variety of cellular states, contributing to GSC heterogeneity and carcinogenesis. The creation of effective therapies may therefore benefit from a better understanding of the factors associated with the GSC's distinct traits as well as the mechanisms affecting GSC cellular states and transformation. Galectin-3 is a molecule that is highly expressed in GBM, and higher levels are linked to poor survival and mesenchymal subtype. Although Galectin-3 has previously been found primarily in microglia and tumor-infiltrating macrophages, our studies using patient-derived GSCs show that it is abundantly produced by GSCs and that its expression significantly decreases when they differentiate into non-stem differentiated cancer cells, which are more responsive to therapies. Our findings also show that Galectin-3 is not expressed in normal neural stem cells, leading us to believe that it could serve as a unique identifier for GSCs. Additionally, when Galectin-3 is silenced in GSCs, we see a decreased self-renewal frequency and enrichment of genes associated with pro-neural state, which has a less aggressive phenotype. Confocal imaging and single-cell RNA-seq analysis further revealed heterogeneous expression of Galectin-3 in GSCs, and the functional pathway analysis shows that Galectin-3high cell clusters have a significant overlap with cells enriched in EMT pathways. Therefore, our findings suggest that Galectin-3 may be a unique distinguishing characteristic of GSCs and may play a particular role in regulating GSC stemness and determining GSCs states, making it a potential molecular target for the treatment of glioblastoma. Citation Format: Bedia Akosman, Shaan Lalvani, Yusuke Suita, David Karambizi, Nikos Tapinos. Galectin-3 regulates stemness and cellular states in glioblastoma stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2448.