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

Keywords

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

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  • Cite this

    Ross, J. A., Vissers, J. P. C., Nanda, J., Stewart, G. D., Husi, H., Habib, F. K., Hammond, D. E., & 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