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Updated: Nov 18, 2025
Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography
Published on: August 16, 2020
Blood-brain barrier alterations in human brain tumors revealed by genome-wide transcriptomic profiling
Johanna Schaffenrath1,2, Tania Wyss3,4, Liqun He5
1Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zürich, Zürich University, Zürich, Switzerland.
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 (EC) isolated from primary and secondary human brain tumors. We used an immunoprecipitation approach to enrich for EC 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 was 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.
Insights
Researchers analyzed endothelial cells from brain tumors to understand blood-brain barrier (BBB) changes. This study identifies potential targets for improved drug delivery across the BBB in brain tumors.
Area of Science:
- Neuro-oncology
- Vascular Biology
- Transcriptomics
Background:
- Brain tumors have limited treatment options, partly due to poor drug delivery across the blood-brain barrier (BBB).
- The tumor stroma, particularly its vasculature, is crucial for tumor growth but remains understudied.
- Understanding brain tumor vasculature is key to overcoming drug delivery challenges.
Purpose of the Study:
- To characterize transcriptional changes in endothelial cells (EC) from primary and secondary human brain tumors.
- To identify molecular targets within the brain tumor vasculature for enhanced drug delivery.
- To investigate the role of vessel-associated fibroblasts in glioblastoma (GBM) stroma.
Main Methods:
- RNA sequencing was used to analyze endothelial cells (EC) isolated from normal brain, glioblastoma (GBM), and lung cancer brain metastasis (BM).
- Immunoprecipitation was employed to enrich for EC from tumor and normal brain tissues.
- Transcriptional profiles of EC and vessel-associated fibroblasts were analyzed.
Main Results:
- Endothelial transcriptomes from GBM and BM showed deregulation of genes involved in cell proliferation, angiogenesis, and extracellular matrix deposition.
- Genes associated with blood-brain barrier (BBB) dysfunction were deregulated in both GBM and BM vasculature.
- Altered gene expression was observed in vessel-associated fibroblasts within GBM.
Conclusions:
- Characterization of BBB gene alterations in GBM and BM vasculature provides potential targets for drug delivery platforms.
- The study highlights the importance of investigating vessel-associated fibroblasts in brain tumor stroma.
- Findings contribute to a better understanding of brain tumor biology and therapeutic strategies.
