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

VIDELA RICHARDSON, GUILLERMO AGUSTÍN; VERA, MARIANA BELÉN; TORRES, NICOLÁS I.; MORRIS HANON, OLIVIA

Congreso; Reunión de Sociedades de Biociencia 2021; 2021

High-grade gliomas exhibit a hierarchical organization that relies on a minor subpopulationof gliomas stem cells (GSC). When injected into immunodeficient mice, these highlytumorigenic cells can develop and propagate brain tumors. GSCs are characterized bytheir self-renewal potential and their differentiation capacity. The use of multiplepatient-derived GSCs constitutes a valuable tool to understand the biology of gliomas ingreater detail and to develop translational projects that might contribute to personalizedtherapies. In the past years, many studies have demonstrated that galectins, a family ofhighly conserved glycan-binding proteins, play key roles in different aspects of cancerbiology, including cellular transformation, proliferation, and apoptosis. In addition, theselectins contribute to tumor progression by favoring angiogenesis, tumor invasion andimmune escape. In this study, we found that patient-derived GSC lines exhibit highexpression 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 -3participate in the control of different processes associated with GSCs. By Ki-67immunostaining, we determined that decreased levels of these galectins lead to areduction in GSC proliferation from 38,8% to 51,6% (p<0.05, n=3). Also, propidium iodidestaining revealed that downregulation of galectin-1 exacerbates cell death in a cellline-specific manner from 76,7% to 126,6% (p<0.05, n=3), and this effect occurs only whengalectin-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 suggeststheir role as potential targets of therapeutic strategies in high-grade gliomas.