Dexamethasone promotes breast cancer stem cells in obese and not lean mice.

Obesity is highly prevalent in breast cancer patients and is associated with increased recurrence and breast cancer-specific mortality. Glucocorticoids (GC) are used as an adjuvant in cancer treatment and are associated with promoting breast cancer metastasis through activation of stemness-related pathways. Therefore, we utilized the synergetic allograft E0771 breast cancer model to investigate if treatment with GCs had differential effects on promoting cancer stem cells in lean and diet-induced obese mice. Indeed, both lean mice treated with dexamethasone and obese mice with no treatment had no effect on the ex vivo colony-forming ability, mammosphere formation, or aldehyde dehydrogenase (ALDH) bright subpopulation. However, treatment of obese mice with dexamethasone resulted in a significant increase in ex vivo colony formation, mammosphere formation, ALDH bright subpopulation, and expression of pluripotency transcription factors. GC transcriptionally regulated genes were not altered in the dexamethasone-treated groups compared to treatment controls. In summary, these results provide initial evidence that obesity presents a higher risk of GC-induced cancer stemness via non-genomic GC signaling which is of potential translational significance.