GSE159851
Blood-brain barrier alterations in human brain tumors revealed by genome-wide transcriptomic profiling
Brain tumors, either primary or secondary, have limited therapeutic options despite advances in understanding tumor driving gene mutations and heterogeneity within tumor cells. The cellular and molecular composition of brain tumor stroma, an important modifier of tumor growth, has been less investigated and understood. Especially, studies focusing on brain tumor blood vessels are rare, yet, the brain endothelium and the blood-brain barrier (BBB) are the major obstacle for efficient drug delivery. In this study we have employed the RNA sequencing approach to get insights into transcriptional alterations of endothelial cells isolated from primary and secondary brain tumors. We used an immunoprecipitation approach to enrich for endothelial cells of normal brain, glioblastoma (GBM) and adenocarcinoma brain metastasis (BM). Analysis of the endothelial transcriptome showed that both the GBM and the BM vasculature showed deregulation of genes implicated in cell proliferation, angiogenesis, deposition of extracellular matrix (ECM), and deregulation of genes defining the BBB dysfunction module. We describe alterations in the BBB genes in the GBM and BM vasculature and identify proteins that could be exploited for developing drug delivery platforms into primary and secondary brain tumors. In addition, we identify deregulated expression of genes defining vessel-associated fibroblasts in the GBM tissue, highlighting that the cellular composition of the brain tumor stroma deserves further investigation. Overall design: Transcriptomic analysis of endothelial cells isolated from primary and secondary brain tumors.