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Updated: Mar 21, 2026
Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Transforming growth factor-β and stem cell markers are highly expressed around necrotic areas in glioblastoma
Yasuo Iwadate1, Tomoo Matsutani2, Seiichiro Hirono2
1Department of Neurological Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-2870, Japan. iwadatey@faculty.chiba-u.jp.
Abstract:
Invasion into surrounding normal brain and resistance to genotoxic therapies are the main devastating aspects of glioblastoma (GBM). These biological features may be associated with the stem cell phenotype, which can be induced through a dedifferentiation process known as epithelial-mesenchymal transition (EMT). We show here that tumor cells around pseudopalisading necrotic areas in human GBM tissues highly express the most important EMT inducer, transforming growth factor (TGF-β), concurrently with the EMT-related transcriptional factor, TWIST. In addition, the stem cell markers CD133 and alkaline phosphatase (ALPL) were also highly expressed around necrotic foci in GBM tissues. The high expression of TGF-β around necrotic regions was significantly correlated with shorter progression-free survival and overall survival in patients with GBM. High expression of stem cell markers, ALPL, CD133, and CD44 was also correlated with poor outcomes. These results collectively support the hypothesis that tissue hypoxia induces the stem cell phenotype through TGF-β-related EMT and contributes to the poor outcome of GBM patients.
Insights
Tissue hypoxia in glioblastoma (GBM) may induce a stem cell phenotype via transforming growth factor-beta (TGF-β)-related epithelial-mesenchymal transition (EMT). This process is linked to increased invasion, therapy resistance, and poorer patient survival outcomes.
Area of Science:
- Neuro-oncology
- Cancer biology
- Molecular pathology
Background:
- Glioblastoma (GBM) is characterized by aggressive invasion and resistance to therapy.
- These aggressive traits may stem from a cancer stem cell phenotype.
- Epithelial-mesenchymal transition (EMT) is a dedifferentiation process implicated in inducing stem cell phenotypes.
Purpose of the Study:
- To investigate the role of hypoxia-induced transforming growth factor-beta (TGF-β) and epithelial-mesenchymal transition (EMT) in glioblastoma (GBM).
- To correlate the expression of EMT markers and stem cell markers with patient outcomes in GBM.
Main Methods:
- Immunohistochemical analysis of human GBM tissues to assess expression of TGF-β, TWIST, CD133, alkaline phosphatase (ALPL), and CD44.
- Correlation analysis between marker expression levels and patient survival data (progression-free and overall survival).
Main Results:
- High expression of TGF-β and the EMT-related transcription factor TWIST was observed around necrotic areas in GBM tissues.
- Stem cell markers CD133 and ALPL were also upregulated around necrotic foci.
- Increased TGF-β expression correlated significantly with shorter progression-free and overall survival.
- Upregulation of stem cell markers (ALPL, CD133, CD44) was associated with poor patient outcomes.
Conclusions:
- Hypoxia in GBM tissues promotes a stem cell phenotype through TGF-β-mediated EMT.
- This hypoxia-driven stem cell phenotype contributes to the aggressive nature and poor prognosis of glioblastoma.
- Targeting hypoxia-induced EMT pathways may offer novel therapeutic strategies for GBM.
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