The influence of hypoxia on the prostate cancer proteome

Ross, James A, Vissers, Johannes PC, Nanda, Jyoti, Stewart, Grant D, Husi, Holger, Habib, Fouad K, Hammond, Dean E ORCID: 0000-0002-6326-8739 and Gethings, Lee A (2020) The influence of hypoxia on the prostate cancer proteome. CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 58 (6). pp. 980-993.

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Abstract

Prostate cancer accounts for around 15% of male deaths in Western Europe and is the second leading cause of cancer death in men after lung cancer. Mounting evidence suggests that prostate cancer deposits exist within a hypoxic environment and this contributes to radio-resistance thus hampering one of the major therapies for this cancer. Recent reports have shown that nitric oxide (NO) donating non-steroidal anti-inflammatory drugs (NSAIDs) reduced tumour hypoxia as well as maintaining a radio-sensitising/therapeutic effect on prostate cancer cells. The aim of this study was to evaluate the impact of hypoxia on the proteome of the prostate and to establish whether NO-NSAID treatment reverted the protein profiles back to their normoxic status. To this end an established hormone insensitive prostate cancer cell line, PC-3, was cultured under hypoxic and normoxic conditions before and following exposure to NO-NSAID in combination with selected other common prostate cancer treatment types. The extracted proteins were analysed by ion mobility-assisted data independent acquisition mass spectrometry (MS), combined with multivariate statistical analyses, to measure hypoxia-induced alterations in the proteome of these cells. The analyses demonstrated that under hypoxic conditions there were well-defined, significantly regulated/differentially expressed proteins primarily involved with structural and binding processes including, for example, TUBB4A, CIRP and PLOD1. Additionally, the exposure of hypoxic cells to NSAID and NO-NSAID agents, resulted in some of these proteins being differentially expressed; for example, both PCNA and HNRNPA1L were down-regulated, corresponding with disruption in the nucleocytoplasmic shuttling process.

Item Type:	Article
Uncontrolled Keywords:	hypoxia, ion mobility, label-free quantitation, liquid chromatography, mass spectrometry, nitric oxide donors, prostate cancer, proteomics
Depositing User:	Symplectic Admin
Date Deposited:	05 Nov 2019 16:37
Last Modified:	19 Jan 2023 00:20
DOI:	10.1515/cclm-2019-0626
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3060666