Defining differential roles for microglia and infiltrating macrophages in the growth and neovascularization of glioma

Abstract

Glioblastoma multiforme, the most common primary malignancy of the central nervous system (CNS), is a highly aggressive and fatal disease. A hallmark of the disease’s pathology is aberrant neovascularization due to inappropriate upregulation of pro-angiogenic signaling pathways within the tumor microenvironment. Signaling via vascular endothelial growth factor (VEGF) is one of the primary aberrant pro-angiogenic pathways in glioma (1). Clinical trials have evaluated the blockade of this pathway with the drug bevacizumab, but failed to produce substantial improvements in patient life expectancy or disease-free progression (2). Due to the complex nature of pathogenic neoangiogenesis in glioma, a primary concern underlying bevacizumab’s lack of efficacy was upregulation of alternative pro-angiogenic pathways within tumors.