ROLE OF GALECTIN-1 IN PATIENT-DERIVED GLIOMA STEM CELLS WITH ENDOTHELIAL FEATURES

RIPARI, LUISINA BELÉN; VERA, MARIANA BELÉN; TORRES, NICOLÁS I.; MORRIS-HANON, OLIVIA; SEVLEVER, GUSTAVO EMILIO; SCASSA, MARÍA ELIDA; RABINOVICH, GABRIEL ADRIÁN; VIDELA RICHARDSON, GUILLERMO AGUSTÍN

Congreso; Reunión Conjunta SAIC. SAI. SAFIS.; 2022

Glioblastoma is the most aggressive type of primary central nervous system (CNS) tumor. These tumors are characterized by high inter-tumoral heterogeneity, which is manifested in the different phenotypes exhibited by patient-derived glioma stem cells (GSC). Notably, it has been reported that GSCs can differentiate even into endothelial cells. Galectin-1 (Gal-1), a β-galactoside-binding protein, has become a potential therapeutic target in different neoplasms since it modulates a myriad of cellular processes such as proliferation, differentiation, migration, and survival. Importantly, Gal-1 triggers immune escape mechanisms in several tumors and promotes angiogenesis in tumors resistant to VEGF-targeted therapies. In our laboratory, we determined that different GSC lines exhibit a high expression of Gal-1 and that its silencing increases cell death and reduces cell proliferation. However, in one of these cell lines (G02), Gal-1 expression does not affect cell viability. RNA-seq showed that this cell line displays a differential expression of several endothelial markers (KDR, ITGA3, ICAM1, EDN1, among others) and exhibits higher amounts of α2-6 sialic acid on its surface, which inhibits Gal-1 binding. We also observed that under hypoxic conditions, many of these endothelial markers increase their expression. Interestingly, an increased expression of Gal-1 and Neuraminidase-1, an enzyme that removes α2-6 sialic acid from cell surfaces, was also observed. Notably, in contrast to normoxic conditions, Gal-1 silencing under hypoxia led to increased cell death in the G02 cell line from 13% to 22% (p0.05, n=3), suggesting that a reduction in α2-6 sialic acid on the cell surface allows the exposure of Gal-1 binding sites and that the binding of this lectin to membrane receptors can promote GSC survival. Therefore, the relevance of Gal-1 in patient-derived GSCs could depend on cell surface α2-6-sialylation and this should be considered when designing tailor-made therapies that target Gal-1.