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Hematogenous dissemination of glioblastoma multiforme
Carolin Müller1, Johannes Holtschmidt2, Martina Auer3
1Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, D-201246 Hamburg, Germany.
Abstract:
Glioblastoma multiforme (GBM) is the most frequent and aggressive brain tumor in adults. The dogma that GBM spread is restricted to the brain was challenged by reports on extracranial metastases after organ transplantation from GBM donors. We identified circulating tumor cells (CTCs) in peripheral blood (PB) from 29 of 141 (20.6%) GBM patients by immunostaining of enriched mononuclear cells with antibodies directed against glial fibrillary acidic protein (GFAP). Tumor cell spread was not significantly enhanced by surgical intervention. The tumor nature of GFAP-positive cells was supported by the absence of those cells in healthy volunteers and the presence of tumor-specific aberrations such as EGFR gene amplification and gains and losses in genomic regions of chromosomes 7 and 10. Release of CTCs was associated with EGFR gene amplification, suggesting a growth potential of these cells. We demonstrate that hematogenous GBM spread is an intrinsic feature of GBM biology.
Insights
Glioblastoma multiforme (GBM) can spread beyond the brain, as evidenced by circulating tumor cells (CTCs) found in patient blood. This discovery challenges previous beliefs about brain tumor dissemination and highlights a potential for hematogenous spread.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor.
- Extracranial metastases from GBM were previously considered rare, often linked to organ transplantation.
- The potential for GBM cells to circulate in the bloodstream was largely unexplored.
Purpose of the Study:
- To investigate the presence and characteristics of circulating tumor cells (CTCs) in patients with Glioblastoma multiforme (GBM).
- To determine if GBM cells can disseminate beyond the central nervous system via the bloodstream.
- To explore potential associations between CTCs and tumor genetics or treatment interventions.
Main Methods:
- Enrichment of peripheral blood mononuclear cells (PBMCs) from GBM patients.
- Immunostaining of PBMCs using antibodies against glial fibrillary acidic protein (GFAP) to identify potential GBM cells.
- Analysis of genetic aberrations (e.g., EGFR amplification, chromosomal gains/losses) in identified GFAP-positive cells.
- Comparison of cell presence in GBM patients versus healthy controls.
Main Results:
- Circulating tumor cells (CTCs), identified by GFAP expression, were detected in 20.6% (29 of 141) of GBM patients.
- The presence of GFAP-positive cells was not significantly increased by surgical intervention.
- Genetic analysis confirmed the tumor origin of GFAP-positive cells, revealing EGFR gene amplification and chromosomal abnormalities characteristic of GBM.
- EGFR gene amplification was associated with the release of CTCs, suggesting their proliferative potential.
Conclusions:
- Hematogenous spread of Glioblastoma multiforme (GBM) is an intrinsic biological feature of the tumor.
- The identification of CTCs in GBM patients challenges the dogma of restricted brain tumor spread.
- Circulating GBM cells possess tumor-specific genetic alterations and may have growth potential, indicating a mechanism for extracranial metastasis.
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