Figure 2.

Crosstalk between BCSCs and stromal cells in the TME. Within the TME, various cell types are known to secrete various cytokines or chemokines such as IL-6, IL-8, CCL2, IL-7, VEGF, etc., that can directly or indirectly influence BCSC function. In addition, different cells within the TME also can promote BCSC expansion via lineage-specific factors. For example: adipocytes secrete adipokine adipsin and leptin that are shown to promote BCSCs; Notch ligands can be produced by endothelial cells, normal epithelial or non-CSC cancer cells, or other stromal cells to promote juxtacrine activation of Notch pathway in BCSCs; and BCSCs can differentiate into endothelial-like cells, which initiates blood vessel formation—a process known as vasculogenic mimicry—and ultimately supports tumor growth.