INTRODUCTION: Glioblastoma is the most common and lethal brain tumour in adults with a mean survival rate of only 12-15 months with current treatment. The microenvironment of a tumour is considered to be essential to tumour pathogenesis. This includes the critical growth factors and cytokines that activate signalling pathways controlling many pro-oncogenic cellular functions. The IL-11 cytokine has become increasingly more important in the pathogenesis of a wide range of cancers, however, very little is known regarding its role in glioblastoma.
METHOD: To study the role of IL-11 in glioblastoma, we first evaluated IL-11 and IL-11R expression in the TCGA database. We also stably transfected IL-11R into 2 patient derived primary glioblastoma cell lines (#20 and #28) to examine the effect of over-expression of IL-11R on Glioblastoma cell proliferation, migration, invasion and survival in glucose and glutamine-depleted conditions.
RESULTS: Analysis of TCGA data identified that IL-11 and IL-11Ra expression correlates with tumour grade and glioblastoma patient survival. Expression of IL-11R also led to an increase in cell proliferation compared to matched control/un-transfected cells. Wound healing and transwell migration assays also demonstrated that IL-11R transfected cell displayed significantly greater migratory ability than control/un-transfected cells. Finally, we demonstrated that cells transfected with the IL-11R could survival in media starved of either glucose or glutamine significantly better than control cells and this enhanced survival was due to reduced activation of cell apoptosis.
CONCLUSION: In conclusion, the data collected suggests interleukin-11 signalling plays a major role in glioblastoma proliferation, migration and survival in sub-optimal conditions.