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

Abstract

Obesity is highly prevalent in breast cancer patients and it is associated with increased recurrence and breast cancer specific mortality. Glucocorticoid (GC) use, in addition to obesity is associated with promoting breast cancer metastasis through activation of stemness-related pathways. Therefore, we utilised 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 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 signalling which is of potential translational significance.