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

J R Packer; A M Hirst; A P Droop; R Adamson; M S Simms; V M Mann; F M Frame; D O'Connell; N J Maitland

doi:10.1002/1873-3468.13589

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

J R Packer, A M Hirst, A P Droop, R Adamson, M S Simms, V M Mann, F M Frame, D O'Connell, N J Maitland

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Number of pages	18
Journal	FEBS Letters
Early online date	30 Aug 2019
DOIs	https://doi.org/10.1002/1873-3468.13589
Publication status	Published - 17 Sept 2019

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10.1002/1873-3468.13589

Packer_et_al-2019-FEBS_Letters
©2019 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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Cite this

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title = "Notch signalling is a potential resistance mechanism of progenitor cells within patient-derived prostate cultures following ROS-inducing treatments",

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.",

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AU - Packer, J R

AU - Hirst, A M

AU - Droop, A P

AU - Adamson, R

AU - Simms, M S

AU - Mann, V M

AU - Frame, F M

AU - O'Connell, D

AU - Maitland, N J

PY - 2019/9/17

Y1 - 2019/9/17

N2 - 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.

AB - 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.

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