Brain tumor cells in circulation are enriched for mesenchymal gene expression

Area of Science:

• Neuro-oncology
• Cancer Biology
• Microfluidics

Background:

• Glioblastoma (GBM) is a highly aggressive brain cancer with limited metastatic potential.
• Understanding GBM cell dissemination is crucial for improving patient outcomes.

Purpose of the Study:

• To investigate the presence and characteristics of circulating tumor cells (CTCs) in GBM patients.
• To explore the potential role of mesenchymal GBM cells in metastasis.

Main Methods:

• Adapted a microfluidic device to isolate circulating brain tumor cells (CTCs) from patient blood.
• Established staining and scoring criteria for GBM CTCs using patient-derived xenografts (PDX).
• Applied criteria clinically and used RNA in situ hybridization to analyze tumor cell markers.

Main Results:

• Identified GBM CTCs in 39% of patients (13 of 33) and 26% of samples (26 of 87).
• Isolated GBM CTCs showed enrichment for mesenchymal differentiation markers.
• Discovered a subpopulation of highly migratory mesenchymal tumor cells within primary GBMs.

Conclusions:

• GBMs shed CTCs with invasive mesenchymal characteristics into the circulation.
• Rare metastatic GBM lesions are primarily mesenchymal and possess distinct mutations.
• A mesenchymal GBM cell subset may invade vasculature and proliferate distantly.