Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy

Area of Science:

• Neuro-oncology
• Cancer Biology
• Molecular Genetics

Background:

• Glioblastoma (GBM) is a deadly brain cancer.
• GBM tumors near the Subventricular Zone (SVZ) are more aggressive.
• Cerebrospinal fluid (CSF) may enhance GBM malignancy.

Purpose of the Study:

• To investigate the impact of human CSF on GBM cells.
• To analyze gene expression changes and their clinical relevance.
• To assess GBM cell proliferation, migration, and tumor growth in response to CSF.

Main Methods:

• Transcriptome analysis of human primary GBM cells exposed to CSF.
• In vitro assessment of GBM cell viability, proliferation, and migration.
• In vivo evaluation of GBM tumor growth after co-injection with CSF.
• Analysis of TCGA database for GBM patient survival prediction.

Main Results:

• CSF induced transcriptomic changes in pathways regulating apoptosis, survival, motility, angiogenesis, inflammation, and glucose metabolism.
• A CSF-induced genetic signature predicted GBM patient survival.
• CSF exposure increased GBM cell viability, proliferation, self-renewal, and migration in vitro.
• In vivo, GBM cells with CSF formed larger, more proliferative tumors.

Conclusions:

• CSF is a key factor in GBM growth and invasion.
• CSF activates gene expression patterns associated with malignancy.
• CSF-induced changes may explain the aggressiveness of SVZ-proximal GBM.
• Findings suggest potential diagnostic and therapeutic strategies for GBM.