Figure 9

Model for DC-sustained cell survival by reduction in ceramide-induced apoptosis in BCPCs. Initially, CD44⁺ stem-like cancer cells are low in ceramide and show asymmetric cell division, giving rise to one stem-like cancer cell and one breast cancer progenitor cell (BCPC). Serum deprivation (growth factor withdrawal) and loss of VEGF receptor (VEGFR) activation leads to increased ceramide levels and the induction of apoptosis in BCPCs. DC induces VEGFR expression, which prevents ceramide elevation and apoptosis in BCPCs, and promotes metastasis and growth of secondary tumors. Apoptosis is restored by blocking the DC receptor FXR with Z-guggulsterone (Z-Gug) or inhibiting VEGFR with SU5416. BCPC, breast cancer progenitor cell; Cer, ceramide; DC, sodium deoxycholate; FXR, farnesoid X receptor; VEGFR, vascular endothelial growth factor receptor;