The influence of hypoxia on the prostate cancer proteome

James A Ross, Johannes P C Vissers, Jyoti Nanda, Grant D Stewart, Holger Husi, Fouad K Habib, Dean E Hammond, Lee A Gethings

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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.

Original languageEnglish
JournalClinical Chemistry and Laboratory Medicine
Early online date15 Jan 2020
DOIs
Publication statusPublished - 2020

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Keywords

  • hypoxia
  • ion mobility
  • label-free quantitation
  • liquid chromatography
  • mass spectrometry
  • nitric oxide donors
  • prostate cancer
  • proteomics

Cite this

Ross, J. A., Vissers, J. P. C., Nanda, J., Stewart, G. D., Husi, H., Habib, F. K., ... Gethings, L. A. (2020). The influence of hypoxia on the prostate cancer proteome. Clinical Chemistry and Laboratory Medicine. https://doi.org/10.1515/cclm-2019-0626