Extracellular redox state regulates features associated with prostate cancer cell invasion

Luksana Chaiswing, Weixiong Zhong, Joseph J. Cullen, Larry W. Oberley, Terry D. Oberley

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

We have examined the possible role of extracellular reduction-oxidation (redox) state in regulation of biological/biochemical features associated with prostate cancer cell invasion. DU145, PC-3, and RWPE1-derived human prostate cancer (WPE1-NB26) cell lines were used for the present in vitro analysis. Increasing levels of nitric oxide using S-nitroso-N-acetylpenicillamine resulted in a decrease in cell invasion ability, whereas increasing levels of extracellular superoxide radical (O2.-) using xanthine/xanthine oxidase resulted in an increase in cell invasion ability in these three cell lines. WPE1-NB26 cells exhibited an increased glutathione/glutathione disulfide ratio in the medium in comparison with RWPE1 cells (immortalized but nonmalignant prostate epithelial cells), suggesting an alteration of extracellular redox state of WPE1-NB26 cells. We hypothesized that O2.- production at or near the plasma membrane or in the adjacent extracellular matrix at least partially regulated prostate cancer cell invasion. Using adenovirus-mediated extracellular superoxide dismutase (ECSOD) gene transduction to enzymatically decrease O2.- levels, we showed that in the presence of heparin, adenovirus ECSOD gene transduction resulted in an increase in the expression of EC-SOD outside the cells with resultant inhibition of cell invasion ability. This inhibition correlated with reduced metalloproteinase [matrix metalloproteinase (MMP) 2/membrane type 1-MMP] activities and increased levels of extracellular nitrite. Our results suggest a prominent role of extracellular redox status in regulation of cell invasion, which may provide opportunities for therapeutic interventions.

Original languageEnglish
Pages (from-to)5820-5826
Number of pages7
JournalCancer Research
Volume68
Issue number14
DOIs
StatePublished - Jul 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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