Tumor Angiogenesis and Glioblastoma Stem Cell Dynamics

Glioblastoma is characterised by an aberrant and highly plastic vasculature that sustains rapid tumour growth and confers therapeutic resistance. New vessel formation arises through multiple, overlapping mechanisms including sprouting angiogenesis, vascular co-option, vasculogenic mimicry and a specialised circumferential process termed vasectasia. Glioblastoma stem cells (GSCs) localise predominantly in perivascular and hypoxic niches where they secrete pro-angiogenic factors such as VEGF and bFGF, transdifferentiate into endothelial-like cells and release extracellular vesicles (EVs) loaded with oncogenic cargo. These EVs remodel endothelial behaviour, perpetuating vicious intercellular feedback loops. Crosstalk between GSCs, endothelial cells and tumour-associated macrophages within a complex microenvironment shapes vessel architecture and promotes adaptive resistance to conventional anti-angiogenic therapies. Elucidating the molecular signals governing GSC-driven neovascularisation is crucial for the development of targeted strategies to normalise tumour vessels and improve patient outcomes.

Research from Nature Portfolio

Recent studies have revealed that mesenchymal GSC subtypes trigger a distinct neovascular process termed vasectasia, driven by EV-mediated transfer of oncogenic EGFR transcripts to endothelial cells. This mechanism underlies persistent vascular enlargement and limits the efficacy of VEGF blockade unless combined with EGFR inhibition. Complementary work has uncovered an endothelial mesenchymal transformation in glioblastoma mediated by a PDGF/NF-κB/Snail axis, which downregulates VEGFR2 expression and confers resistance to anti-VEGF therapy. Dual inhibition of VEGF and PDGF pathways re-sensitises tumour endothelium, disrupts mesenchymal traits and prolongs survival in preclinical models, highlighting vascular de-transformation as a promising therapeutic strategy.

Tumor Angiogenesis and Glioblastoma Stem Cell Dynamics publication trend

The graph below shows the total number of articles in tumor angiogenesis and glioblastoma stem cell dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Angiogenesis: Formation of new blood vessels from existing vasculature, driven by coordinated endothelial cell proliferation, migration and tube formation.

Vasectasia: Circumferential expansion of existing vessels induced by tumour signals, distinct from sprouting angiogenesis.

Glioblastoma stem cells (GSCs): Self-renewing tumour cell subpopulation that initiates and sustains glioblastoma growth and contributes to vascular remodelling.

Extracellular vesicles (EVs): Nano-sized, membrane-bound particles released by cells, carrying proteins and nucleic acids that alter the behaviour of recipient cells.

Perivascular niche: Microenvironment adjacent to blood vessels providing GSCs with signals that maintain their stemness, promote invasion and support angiogenesis.

References

1. Mesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR. Nature Communications (2024).
2. IFITM3 promotes glioblastoma stem cell-mediated angiogenesis via regulating JAK/STAT3/bFGF signaling pathway. Cell Death & Disease (2024).
3. KDELC2 Upregulates Glioblastoma Angiogenesis via Reactive Oxygen Species Activation and Tumor-Associated Macrophage Proliferation. Antioxidants (2023).
4. PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma. Nature Communications (2018).