(A833) Hypoxia Effects on Cell Viability and Cytokine Secretion in Vestibular Schwannoma and Human Schwann Cells

Introduction: Vestibular schwannomas (VS) are benign tumors that cause hearing loss and dizziness. Although many cancers have developed adaptive mechanisms to support cell survival and proliferation in hypoxic environments, the effect of hypoxia on cell proliferation and cytokine secretion in normal Schwann cells (SCs) and VS cells is not well understood.

Methods: Patient-derived VS cells and normal human SCs were cultured in hypoxic (5% O2) or normoxic (21% O2) conditions. Viability assays and cytokine array analyses were performed at 72 hours. Results were compared between cell types and oxygen conditions. Two sample t-tests and descriptive statistics were performed.

Results: Although hypoxia caused a significant reduction in viability of normal SCs (p < 0.0001), we observed a significant increase in viability of VS cells in hypoxia when compared to normoxia (p < 0.001). In hypoxic conditions, normal SCs secreted higher levels of insulin-like growth factor binding protein-6 and tissue inhibitor of metalloproteinases 1 (TIMP1) while VS cells secreted more interleukin-8 (IL-8) and TIMP1.

Conclusions: Hypoxia induced cell proliferation in VS may be related to upregulation of IL-8, which is a cytokine that promotes cell proliferation and angiogenesis in several cancers. We also demonstrated that normal SCs and VS cells upregulate TIMP1 in hypoxic conditions, which is a protein that has been shown to protect against neuronal death after hypoxic insults. Additional studies are warranted to further elucidate how hypoxia affects individual VS and related immune cells within the tumor microenvironment, which can lead to the identification of novel therapies for VS.