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

Abstract 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‐...

Full description

Saved in:
Bibliographic Details
Main Authors: Stephanie Annett (Author), Orla Willis Fox (Author), Damir Vareslija (Author), Tracy Robson (Author)
Format: Book
Published: Wiley, 2022-04-01T00:00:00Z.
Subjects:
Online Access:Connect to this object online.
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract 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.
Item Description:2052-1707
10.1002/prp2.923