Characterization of aberrant glycosylation in human glioma cell lines

CUELLO, HÉCTOR A.; MAGALI GRETEL FERREYRA; GULLINO C; SEGATORI VALERIA INÉS; GABRI MARIANO R

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Gliomas are the most common and aggressive primary brain tumor in adults. It accounts for 45.6% of primary malignant brain tumors. New therapeutic targets are needed for this indication since patient?Ls survival after current therapy is 2 years. Glycosylation reflects the coordinated effort of a complex array of glycosyltransferases (GST) to successfully generate carbohydrate-associated posttranslational modifications. The aberrant glycosylation is a key actor in crucial processes for cancer cells survival and it is a direct consequence of the deregulation of GST?Ls expression. Even when gliomas represent the intracranial neoplasm of greater incidence and aggressiveness, little is known about their profile of glycosylation and its participation in the malignant phenotype. The objective of this work is the characterization of the glycophenotype of four human glioma cell lines by studying cancer associated glycans expression, glycans ramifications, enzymes expression and their impact in cell behaviour. High and medium expression of terminal glycans SleX and LeY were found in LN229, U87MG, U251 and U373 cell lines measured by FACS.The evaluation of glycan branching structures by lectin binding showed higher expression of ?À-1,6 ramifications and bisected N-glycans in U373 and LN229 in relation to U87MG and U251. These structures are associated with an overexpression of the glycosyltransferases MGAT5 and MGAT3, measured by qRT-PCR. Tunicamycin treatment suggested that described glycans are part of N-linked structures. Furthermore, Tunicamycin treatment provoked a significant decrease in cell adhesion and migration in vitro. In conclusion, the four cell lines evaluated present high expression of Lewis family glycans -mainly SLeX and LeY- with N-glycan type ramifications based on the activity of the enzymes MGAT5 and MGAT3. The glycophenotype study in cellular models constitute a value tool for the identification of novel therapeutic targets in Glioma.