Figure 1. Niche contributes to the maintenance of CSCs.

Niche is composed of cancer cells, various non-cancer cells, as well as physical and biochemical factors that maintain CSCs. Tumor-associated macrophages exert influence on CSCs by direct contact or through soluble factors such as EGF and ISG15. Mesemchymal stem cells secrete cytokines such as PGE₂, IL-6, IL-8, and Gro-α. Endothelial cells and vessels provide nutrition and oxygen to support CSCs. In turn, CSCs produce VEGF and SDF1 to stimulate angiogenesis. Cancer-associated fibroblasts release a variety of growth factors, chemokines, and components of the ECM into niche, such as AnxA1, IGF-II, HGF, LIF, and SDF1. In addition, hypoxia can also contribute to the maintainence and formation of CSCs.