Aberrant glycosylation in nervous system tumors

HECTOR A. CUELLO; GRETEL MAGALÍ FERREIRA; CYNTHIA A. GULINO; MARINA ALBERTÓ; ROSARIO ASCHERO; LAURA GALLUZZO MUTTI; DANIEL F. ALONSO; FABIANA LUBIENIECKI; VALERIA I. SEGATORI; MARIANO R. GABRI

San Diego

Simposio; 22nd Annual San Diego Glycobiology Symposium (SDGS); 2019

Glycans have a crucial participation in critical events of cell biology. Little is knownabout their role in neural cancers such as Neuroblastoma (NB) and Glioma. NB is themost common pediatric malignancy diagnosed before the first birthday and Gliomasrepresent the intracranial neoplasm of greater incidence and aggressiveness. Theobjective of this work is to characterize their glycophenotype using human cell linesand patients´ samples.In NB there is an association between aggressiveness (MYCN gene amplification) andLewis glycans expression in cell lines and patients´ samples. MYCN-amplified cellsoverexpress Core 2-initiating glycosyltransferase C2GNT1 in association with specificST3Gals and FUTs. Core2-O glycans seem to play a role in NB since silencing of C2GNT1provoked a decreased in vitro cell adhesion, migration and proliferation. Furthermore,Lewis glycans expression is regulated by epigenetic mechanisms stemming from anincrease in glycans and fucosyltransferases expression of MYCN-non-amplified cellsafter histone deacetylase inhibitor treatment.Gliomas patients´ samples overexpress Le x , SLe x , Le a and T antigens (79%, 37%, 43.75%,100% respectively). High and medium expression of Sle x and Le y were found in LN229,U87MG, U251 and U373 cells. N-Glycans seem to be relevant for Glioma sinceTunicamycin treatment provoked a significant decrease in in vitro cell lines adhesion.The evaluation of N-glycan branching structures by lectin binding showed higherexpression of β-1,6 ramifications and bisected N-glycans in U373 and LN229, structuresassociated with an overexpression of MGAT5 and MGAT3. The study of aberrantglycosylation is a promising field for the identification of novel therapeutic targets.