Distinct responses of patient-derived GBM cell lines to hypoxia
Glioblastoma (GBM) is the most common primary malignant cancer of the central nervous system. Hypoxia, low oxygen, has been linked to GBM infiltration and aggressive tumor progression leading to poor patient outcome. Hypoxia-induced pathways are activated by the stabilization of HIF1-a, which upregulates genes related to reprogramming metabolism, angiogenesis, cell trafficking, and cell survival. However, underlying mechanisms of HIF-1a involvement with GBM cell specific pathways is not fully understood. Here, we show that hypoxia can induce specific genes dependent on GBM subtype. In a in vitro migration assay, we screened eight patient-derived GBM stem cell lines. Two lines, UCA and UNB, were found to induce an increased migration ability in response to hypoxia. By RNA bulk sequencing, we identified key specific genes that were upregulated in each cell line that were not shared between them. Furthermore, we found that this data set correlates to previous single-cell RNA sequencing findings of GBM having differentiated transcriptional subtypes. Our results demonstrate how hypoxia induces a specific response in tumor cells by activating genes for survival and tumor progression. Our study forms the basis for future approaches to characterize top candidate genes and elucidate their role in tumor survival in response to hypoxia. Inhibition of these top candidate genes can be a strategy used to dampen hypoxia pro-tumor properties and may lead to better outcomes for GBM patients. Overall design: 3 replicates of UCA vs. 3 replicates of UNB exposed to either normoxia (UCA_NORM and UNB_NORM) or hypoxia (UCA_HYPO and UNB_HYPO) for 72h before extracting RNA for RNA bulk.