Article Dans Une Revue Neuro-Oncology Année : 2024

P18.38.A ROLE OF CARBOHYDRATE-BINDING PROTEINS IN CONTROLLING GLIOBLASTOMA STEM CELL FATE AND TUMORIGENESIS

Résumé

Abstract BACKGROUND Carbohydrate-binding proteins, galectins (GAL, LGALS), is a family of proteins that specifically bind β-galactoside sugars. Some members of the GAL family have been shown to be associated with tumor development, including glioblastoma (GB). However, their precise role is poorly investigated. MATERIAL AND METHODS Publicly available data sets were analyzed with SUMO software. scRNA-seq data analysis was conducted with the R toolkit Seurat and SingleR package. For in vitro experiments, patient-derived glioblastoma stem cells (GSCs) BTSC73 and BTSC12 were used as cellular models. Differentiation was induced by culturing GSCs on laminin-coated plates in media supplemented with 10% FBS. Hypoxia-response was studied at 1% O2. For depletion experiments siRNA silencing was used as well as CRISPR-Cas9. Proliferation was assessed by EDU staining. Cell death was assessed using Annexin/PI double staining assay. RESULTS We first conducted an in silico analysis for LGALS1, -3, -8, and -9 expression in GB. We found that specific combinations of these Galectins are associated with a poor prognosis. In GB patients. When scRNASeq data were analyzed, Galactins are distributed heterogeneously in different cell types in the tumor. For example, Gal3 is expressed in tumor cells, macrophages, and T-cells. We then conducted in vitro experiments to assess the role of Gal3 and Gal9. Depletion of LGALS3 in BTSC73 led to a decrease in cell number related to an effect on proliferation but not apoptosis. In addition, LGALS3 depletion in GSCs reduced stemness markers such as Sox2 and Nestin. We also investigated LGALS3 and LGALS9 expression during differentiation and found their expression increased which was also the case under hypoxia. CONCLUSION This indicates that Gals and especially Gal3 and Gal9 are involved in GB development including, proliferation stemness and differentiation.
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hal-04833233 , version 1 (12-12-2024)

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M Sliusar, L Chaillot, A Burban, A Sharanek, A Bikfalvi. P18.38.A ROLE OF CARBOHYDRATE-BINDING PROTEINS IN CONTROLLING GLIOBLASTOMA STEM CELL FATE AND TUMORIGENESIS. Neuro-Oncology, 2024, 26 (Supplement_5), pp.v106-v106. ⟨10.1093/neuonc/noae144.354⟩. ⟨hal-04833233⟩

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