Vascular endothelial growth factor in astroglioma stem cell biology and response to therapy: Stem Cells Review Series

Abstract

Introduction Adult brain - a dynamic structure with active stem cells? Cancer stem-like cells in brain tumours Angiogenesis in astrogliomas VEGF and the 'stem cell niche' Resistance to DNA-damaging therapy in astrogliomas VEGF and DNA damage response: implications for astroglioma therapy 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. © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.