(176a) Direct Contact with Astrocytes Drives Metabolic Reprogramming in Glioma Cells

Glioblastoma Multiforme (GBM) is the most prolific and deadly malignant brain tumor in the United States with an age-adjusted incidence rate of 3.2 cases per 100,000 population and more than 13,000 cases projected in 2020. The median survival time after GBM diagnosis is less than 18 months and fewer than 7% of patients exhibit long-term survival greater than 5 years. GBMs arise from astrocytes or other glial cells and are characterized by their invasion into surrounding tissues and recruitment of healthy tissues into tumor tissue. Astrocytes, the most abundant glial cell in the brain, primarily function to maintain ion homeostasis and modulate energy production through both direct and indirect communication. Modulation of GBM cell metabolism is associated with the aggressiveness, and thereby mortality, associated with the tumor, however the underlying mechanisms that attribute to distinct aspects of GBM metabolism remain unknown. Here, we demonstrate that the physical contact of GBM cells with astrocytes is a potential modulator of metabolic reprogramming in glioma cells. Using layer-by-layer assembly and microcapillary-force driven in vitro patterning, we have engineered a glioma/astrocyte co-culture model, wherein we find that physical contact with astrocytes results in significant upregulation in energy utilization of glioblastoma cells when grown in co-culture with astrocytes compared to both transwell co-culture and glioma cells grown in monoculture. Beyond this, we also show a significant change in metabolism-related and signaling-related proteins and a significant upregulation of the transcription of genes involved in energy metabolism. Taken together, these results indicate a more aggressive glioma phenotype when cells are in physical contact with astrocytes thereby suggesting that astrocytes are potent mediators of metabolic reprogramming in glioma cells and could reveal targets to treat GBM patients.