Tumor (SVZ) micro-environment

The tumor (SVZ) micro-environment. GICs (light purple) are regulated by the activation of oncogenes or by environmental conditions such as hypoxia or acidosis. GICs are able to express pro-angiogenic factors, such as VEGF (vascular endothelial growth factor), able to stimulate the outgrowth of new blood vessels (red) which will in the end help to maintain tumorigenicity. Endothelial cells are also able to produce nitric oxide in the endothelium through the activation of eNOS. Activated Notch signaling by nitric oxide in GICs is notably known to accelerate tumor progression. Defects in growth factor signaling pathways usually result in the activation of downstream growth factor signaling such as the PI3K/Akt signaling pathway which has been shown to be an important regulator of glioma cell survival and GICs’ radioresistant abilities. Neural progenitor cells (yellow) display antitumor effects by secreting tumor suppressors in the niche such as bone morphogenetic protein-7 (BMP7), inducing GICs’ differentiation. Astrocytes (dark blue) are closely associated with the vascular endothelium of the niche and were shown to secrete neurotrophic factors capable of driving the invasive properties of GBM cells (CXCL12, SIP, and GDNF). Astrocytes also express high levels AEG-1. Reports suggest that AEG-1 impacts on brain tumor invasion notably through the activation of MMP-2 and MMP-9.

Publication

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment. (2013) Nicolas Goffart, et al. Cancers (Basel). 2013 Sep;5(3):1049-1071. Figure: F2. All organisms Homo sapiens Mus musculus Rattus norvegicus

Disease mentions