Ross, J. A., Vissers, J. P.C., Nanda, J., Stewart, G. D., Husi, H., Habib, F. K., Hammond, D. E. and Gethings, L. A. (2020) The influence of hypoxia on the prostate cancer proteome. Clinical Chemistry and Laboratory Medicine, 58(6), pp. 980-993. (doi: 10.1515/cclm-2019-0626) (PMID:31940282)
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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: | Articles |
|---|---|
| Keywords: | Hypoxia, ion mobility, label-free quantitation, liquid chromatography, mass spectrometry, nitric oxide donors, prostate cancer, proteomics. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Husi, Dr Holger |
| Authors: | Ross, J. A., Vissers, J. P.C., Nanda, J., Stewart, G. D., Husi, H., Habib, F. K., Hammond, D. E., and Gethings, L. A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Clinical Chemistry and Laboratory Medicine |
| Publisher: | Walter de Gruyter |
| ISSN: | 1434-6621 |
| ISSN (Online): | 1437-4331 |
| Published Online: | 15 January 2020 |
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