Blood-brain barrier alterations in human brain tumors revealed by genome-wide transcriptomic profiling.

BACKGROUND Brain tumors, whether primary or secondary, have limited therapeutic options despite advances in understanding driver 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 to date. Only few studies have focused on the vasculature of human brain tumors despite the fact that the blood-brain barrier (BBB) represents the major obstacle for efficient drug delivery. METHODS In this study, we employed RNA sequencing to characterize transcriptional alterations of endothelial cells isolated from primary and secondary human brain tumors. We used an immunoprecipitation approach to enrich for endothelial cells from normal brain, glioblastoma (GBM) and lung cancer brain metastasis (BM). RESULTS Analysis of the endothelial transcriptome showed deregulation of genes implicated in cell proliferation, angiogenesis and deposition of extracellular matrix (ECM) in the vasculature of GBM and BM. Deregulation of genes defining the BBB dysfunction module were found in both tumor types. We identified deregulated expression of genes in vessel-associated fibroblasts in GBM. CONCLUSION We characterize alterations in BBB genes in GBM and BM vasculature and identify proteins that might be exploited for developing drug delivery platforms. In addition, our analysis on vessel-associated fibroblasts in GBM shows that the cellular composition of brain tumor stroma merits further investigation.