PO-367 Brain microenvironment-secreted cytokines facilitate glioblastoma proliferation and invasion

Abstract

IntroductionGlioblastoma is the most common and lethal type of brain cancer with a median survival of under fifteen months. It is a highly angiogenic tumour exhibiting an extremely invasive nature. It is well-known that the brain microenvironment plays a crucial role in glioblastoma progression although the large multitude of interactions between the cancer cells and their microenvironment are yet to be fully unravelled. Astrocytes are the most abundant glial cells in the brain and have been shown to be involved in many types of brain pathologies as well as metastatic colonisation in the brain. Hence, we investigated the influence of astrocytes on the migratory and infiltrative abilities of glioblastoma cells.Material and methodsIn order to evaluate the influence of brain microencironment on glioblastoma progression we used co-culture proliferation and migration assays as well immunohistochemistry analysis of our mouse models and patient derived samples. Using protein profiler we assessed the level of cytokines secreted following interaction of glioblastoma cells and their microenvironment.Results and discussionsUsing in vitro and ex vivo assays, we found that in the presence of either astrocytes or their conditioned media, the migration rate of glioblastoma cells is significantly increased. Microglia are macrophages-like cells which possess antigen-presenting and phagocytic abilities that serve as the brain immune system. In a co-culture proliferation assay, we observed that microglia increased glioblastoma cells proliferation at a concentration-dependent manner. Furthermore, co-culture of glioblastoma cells with either astrocytes, microglia or brain endothelial cells resulted in elevated levels of several similar cytokines. Moreover, immunohistochemistry analysis of several brain tumours inoculated orthotopically in mice revealed an increased level of activated astrocytes and microglia and high microvessel density within the tumoursiteConclusionOur findings indicate that the brain microenvironment facilitates glioblastoma proliferation and invasion by cytokines secretion paving the way for investigation of their use as targets for glioblastoma therapy.