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Vascular endothelial growth factor in astroglioma stem cell biology and response to therapy
Petra Knizetova1, John L Darling, Jiri Bartek
1Laboratory of Molecular Pathology, Institute of Pathology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic. knizetko@yahoo.com
Abstract:
Malignant astrogliomas are among the most aggressive, highly vascular and infiltrating tumours bearing a dismal prognosis, mainly due to their resistance to current radiation treatment and chemotherapy. Efforts to identify and target the mechanisms that underlie astroglioma resistance have recently focused on candidate cancer stem cells, their biological properties, interplay with their local microenvironment or 'niche', and their role in tumour progression and recurrence. Both paracrine and autocrine regulation of astroglioma cell behaviour by locally produced cytokines such as the vascular endothelial growth factor (VEGF) are emerging as key factors that determine astroglioma cell fate. Here, we review these recent rapid advances in astroglioma research, with emphasis on the significance of VEGF in astroglioma stem-like cell biology. Furthermore, we highlight the unique DNA damage checkpoint properties of the CD133-marker-positive astroglioma stem-like cells, discuss their potential involvement in astroglioma radioresistance, and consider the implications of this new knowledge for designing combinatorial, more efficient therapeutic strategies.
Insights
Malignant astrogliomas resist treatment due to cancer stem cells. Vascular endothelial growth factor (VEGF) and DNA damage checkpoints in CD133+ cells are key to astroglioma radioresistance and recurrence.
Area of Science:
- Neuro-oncology
- Cancer Stem Cell Biology
- Molecular Oncology
Background:
- Malignant astrogliomas are aggressive brain tumors with poor prognosis, often resistant to standard therapies.
- Cancer stem cells (CSCs) and their microenvironment are implicated in tumor progression and treatment resistance.
- Vascular endothelial growth factor (VEGF) plays a crucial role in regulating astroglioma cell behavior through paracrine and autocrine signaling.
Purpose of the Study:
- To review recent advances in astroglioma research, focusing on the role of VEGF in CSC biology.
- To highlight the DNA damage checkpoint properties of CD133+ astroglioma stem-like cells.
- To discuss the implications for developing novel therapeutic strategies against astroglioma.
Main Methods:
- Literature review of recent studies on astroglioma, cancer stem cells, VEGF, and DNA damage checkpoints.
- Analysis of the biological properties and microenvironmental interactions of astroglioma stem-like cells.
- Synthesis of findings to evaluate the role of VEGF and CD133+ cells in radioresistance.
Main Results:
- VEGF is a key regulator of astroglioma CSC behavior and fate.
- CD133-positive astroglioma stem-like cells exhibit unique DNA damage checkpoint mechanisms.
- These properties contribute significantly to astroglioma's resistance to radiation therapy.
Conclusions:
- Understanding VEGF's role in CSCs is critical for astroglioma treatment.
- Targeting DNA damage checkpoints in CD133+ CSCs offers a promising therapeutic avenue.
- Combinatorial strategies incorporating these findings may improve treatment efficacy for malignant astrogliomas.
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