Role of glycosylation in the interaction between integrin 𝛼v and urokinase plasminogen activator receptor in human glioblastoma

NOGUEIRA AYLÉN CAMILA; FERREIRA GRETEL MAGALÍ; ROJO; GULINO CYNTHIA ANTONELLA; CASTILLO JEREMÍAS OMAR; SEGATORI VALERIA INÉS; GABRI MARIANO ROLANDO

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

It is well described that aberrant glycosylation has an important rolenot only in tumor transformation but also in tumor progression. Glio-blastoma (GBM) has a median survival of 15 months and a long-termsurvival of less than 5% in human patients. This poor patient survivalpoints out the importance of new therapeutics targets to be discov-ered in this type of tumors. Integrin alpha V (IαV) and urokinase-typeplasminogen activator receptor (uPAR) are glycosylated plasmamembrane proteins described as key players in GBM malignancy.Even though IαV has been reported to act as a co-receptor of uPAR,there is no information regarding how these two proteins interactwith each other in GBM. Taking this information into account, the aimof our work was to evaluate if the interaction between them in GBMis mediated by glycans and to identify which type of glycosylation isinvolved. We first evaluated the expression of IαV and uPAR on aset of human GBM cell lines by flow cytometry, and found that the4 cell lines showed expression of both proteins with mean fluores-cence values of 9,56 ± 3,82 and 1,36 ± 0,2, respectively. Since A172cells showed the higher expression of uPAR, we decided to continuethe experiments using this cell line as our model. In order to increaseuPAR expression, at the same time we transfected A172. We thenevaluated the interaction between IαV and uPAR in A172 wild typecells by co-immunoprecipitation, and found that both protein interactsince the pull down of IαV allows us to observe the presence ofuPAR by western blot. Interestingly, swainsonine treatment disruptsthis interaction. These results suggest that N-glycans may have arole in the interaction between IαV and uPAR in GBM, laying thefoundation for further characterize and evaluate how N-glycosylationmodulates downstream signaling and tumor behavior.