Dexamethasone promotes breast cancer stem cells in obese and not lean mice.pdf (1.41 MB)
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Dexamethasone promotes breast cancer stem cells in obese and not lean mice

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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.

Funding

Susan G. Komen

History

Comments

The original article is available at https://bpspubs.onlinelibrary.wiley.com/ Pre-print is available on bioRxiv https://doi.org/10.1101/2021.06.18.449008 & RCSI repository https://hdl.handle.net/10779/rcsi.15117123

Published Citation

Annett S, Fox OW, Vareslija D, Robson T. Dexamethasone promotes breast cancer stem cells in obese and not lean mice. Pharmacol Res Perspect. 2022;10(2):e00923

Publication Date

14 March 2022

PubMed ID

35289104

Department/Unit

  • School of Pharmacy and Biomolecular Sciences
  • Surgery

Publisher

John Wiley & Sons Ltd

Version

  • Published Version (Version of Record)