Biological relevance of galectins in patient-derived glioma stem cells and their potential application in the development of personalized antineoplastic strategies

GUILLERMO A. VIDELA RICHARDSON; MARIANA BELÉN VERA; NICOLÁS IGNACIO TORRES; LUISINA BELÉN RIPARI; OLIVIA MORRIS HANON; MYRIAN INÉS ESQUIVEL; GUSTAVO E. SEVLEVER; GABRIEL A. RABINOVICH

Congreso; Reunión Conjunta SAIC. SAI. AAFE. NANOMED.ar.; 2021

High-grade gliomas exhibit a hierarchical organization that relies on a minor subpopulation of gliomas stem cells (GSC). When injected into immunodeficient mice, these highly tumorigenic cells can develop and propagate brain tumors. GSCs are characterized by their self-renewal potential and their differentiation capacity. The use of multiple patient-derived GSCs constitutes a valuable tool to understand the biology of gliomas in greater detail and to develop translational projects that might contribute to personalized therapies. In the past years, many studies have demonstrated that galectins, a family of highly conserved glycan-binding proteins, play key roles in different aspects of cancer biology, including cellular transformation, proliferation, and apoptosis. In addition, these lectins contribute to tumor progression by favoring angiogenesis, tumor invasion and immune escape. In this study, we found that patient-derived GSC lines exhibit high expression of galectins-1 and -3 and an intermediate expression of galectins-2, -8, and -9. Importantly, by siRNA-mediated gene silencing, we found that galectins-1 and -3 participate in the control of different processes associated with GSCs. By Ki-67 immunostaining, we determined that decreased levels of these galectins lead to a reduction in GSC proliferation from 38,8% to 51,6% (p0.05, n=3). Also, propidium iodide staining revealed that downregulation of galectin-1 exacerbates cell death in a cell line-specific manner from 76,7% to 126,6% (p0.05, n=3), and this effect occurs only when galectin-3 expression is unaltered. Finally, as shown by cell spreading migration assays, silencing of these galectins also impairs GSC migration from 17% to 48% (p0.05, n=3). Thus, involvement of these lectins in multiple processes associated with GSCs suggests their role as potential targets of therapeutic strategies in high-grade gliomas.