Role of neural cancer stem cells in angiogenesis

Growing evidence indicates the existence of small population of cells endowed with distinctive self-renewal capacity, tumorigenesis and resistance to conventional treatments, defined as cancer stem cells (CSCs) or tumor initiating cells. In addition, it is widely appreciated that the growth of new blood vessels and lymphatic vasculature, which occurs during angiogenesis and limphoangiogenesis, plays a key role in the process of the tumor growth. To this regards, an increasing number of studies showed that the employment of angiogenesis inhibitors might have significant therapeutic advantages. Fashinatingly, recent evidence demonstrated that CSCs play a role in angiogenesis, in particular in glioma, which, to date, represents a highly letal tumor tough to treat. We demonstrated that CSCs isoleted from both tumor (GCSCs) and peritumoral tissue (PCSCs) express a number of angiogenesis-related molecules, such as VEGF, HIF1alpha and HIF2alpha. In addition, VEGFR1 expression was found significantly reduced in PCSCs vs GCSCs whereas VGFR2 appeard to be largely heterogeneous in both stem cell types. With the aim to investigate the aptitude of CSCs derived neurospheres to regulate the angiogenesis process we performed in vitro migration analysis by means of boiden chamber assay. The results of this experiments indicate that ECs migration was stimulated in the presence of PCSCs but remained almost unaffected when endothelial cells where co-coltured with GCSCs. In conclusion, our data suggest that GCSCs and PCSCs contribute differently to tumor angiogenesis by activating distinct molecular mechanisms. PCSCs might therefore a key role in the recruiment as well as activation of ECs in peritumoral tissue.