Figure 4.

The vascular cancer stem cell niche. The process of angiogenesis is a normal homeostatic process in healthy individuals; however, it is also a necessary process for primary tumor growth. CSCs, as demonstrated in the neural stem cell niche, reside within in close proximity to tumor blood vessels and promote angiogenesis. Angiogenesis is stimulated by a hypoxic environment as well, therefore, HIF1, is capable of mediating VEGF receptors expressed on the surface of CSCs. The activation of VEGF results in the activation of angiogenic regulators such as FGFs, PDGF and EGFs as well. Additionally, tissue factor (TF) receptors, hypothesized to exist on the surface of CSCs, promote growth, survival, migration and a proangiogenic phenotype. TF has been shown to upregulate critical CSC regulators such as Nanog, Oct4, Kl5 and LIF which can promote CSC maintenance within a vascular CSC niche.