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Notch signalling is a potential resistance mechanism of progenitor cells within patient‐derived prostate cultures following ROS‐inducing treatments
Author(s) -
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.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13589
Subject(s) - progenitor cell , prostate cancer , notch signaling pathway , cancer research , context (archaeology) , microbiology and biotechnology , prostate , biology , reactive oxygen species , long term potentiation , signal transduction , chemistry , stem cell , cancer , biochemistry , receptor , genetics , paleontology
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.