Notch signalling is a potential resistance mechanism of progenitor cells within patient‐derived prostate cultures following ROS‐inducing treatments

Packer, John R.; Hirst, Adam M.; Droop, Alastair P.; Adamson, Rachel; Simms, Matthew S.; Mann, Vincent M.; Frame, Fiona M.; O'Connell, Deborah; Maitland, Norman J.

Abstract

Low Temperature Plasma (LTP) generates reactive oxygen and nitrogen species, causing cell death, similarly to radiation. Radiation resistance results in tumour recurrence, however mechanisms of LTP resistance are unknown. LTP was applied to patient‐derived prostate epithelial cells and gene expression assessed. A typical global oxidative response (AP‐1 and Nrf2 signalling) was induced, whereas Notch signalling was activated exclusively in progenitor cells. Notch inhibition induced expression of prostatic acid phosphatase (PAP), a marker of prostate epithelial cell differentiation, whilst reducing colony forming ability and preventing tumour formation. Therefore, if LTP is to be progressed as a novel treatment for prostate cancer, combination treatments should be considered in the context of cellular heterogeneity and existence of cell type‐specific resistance mechanisms.

Citation

Packer, J. R., Hirst, A. M., Droop, A. P., Adamson, R., Simms, M. S., Mann, V. M., …Maitland, N. J. (2019). Notch signalling is a potential resistance mechanism of progenitor cells within patient‐derived prostate cultures following ROS‐inducing treatments. FEBS Letters, https://doi.org/10.1002/1873-3468.13589

• Journal Article Type: Article
• Acceptance Date: Aug 8, 2019
• Online Publication Date: Aug 30, 2019
• Publication Date: Aug 30, 2019
• Deposit Date: Nov 8, 2019
• Publicly Available Date: Nov 11, 2019
• Journal: FEBS Letters
• Print ISSN: 0014-5793
• Electronic ISSN: 1873-3468
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1002/1873-3468.13589
• Keywords: Low temperature plasma; Notch signalling; Progenitor cells; Prostate cancer; Reactive oxygen species; Therapy resistance
• Public URL: https://hull-repository.worktribe.com/output/3114650
• Publisher URL: https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.13589
• Related Public URLs: http://eprints.whiterose.ac.uk/150977/
• Additional Information: Received: 2019-05-29; Accepted: 2019-08-08; Published: 2019-09-17