Altered redox status accompanies progression to metastatic human bladder cancer

Nadine Hempel, Hanqing Ye, Bryan Abessi, Badar Mian, J. Andres Melendez

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The role of reactive oxygen species (ROS) in bladder cancer progression remains an unexplored field. Expression levels of enzymes regulating ROS levels are often altered in cancer. A search of publicly available microarray data reveals that expression of mitochondrial manganese superoxide dismutase (Sod2), responsible for the conversion of superoxide (O2{radical dot}-) to hydrogen peroxide (H2O2), is consistently increased in high-grade and advanced-stage bladder tumors. We aimed to identify the role of Sod2 expression and ROS in bladder cancer. Using an in vitro human bladder tumor model we monitored the redox state of both nonmetastatic (253J) and highly metastatic (253J B-V) bladder tumor cell lines. 253J B-V cells displayed significantly higher Sod2 protein and activity levels compared to their parental 253J cell line. The increase in Sod2 expression was accompanied by a significant decrease in catalase activity, resulting in a net increase in H2O2 production in the 253J B-V cell line. Expression of the prometastatic and proangiogenic factors matrix metalloproteinase 9 (MMP-9) and vascular endothelial-derived growth factor (VEGF), respectively, was upregulated in the metastatic line. Expression of both MMP-9 and VEGF was shown to be H2O2-dependent, as removal of H2O2 by overexpression of catalase attenuated their expression. Similarly, expression of catalase effectively reduced the clonogenic activity of 253J B-V cells. These findings indicate that metastatic bladder cancer cells display an altered antioxidant expression profile, resulting in a net increase in ROS production, which leads to the induction of redox-sensitive protumorigenic and prometastatic genes such as VEGF and MMP-9.

Original languageEnglish (US)
Pages (from-to)42-50
Number of pages9
JournalFree Radical Biology and Medicine
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2009

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Urinary Bladder Neoplasms
Oxidation-Reduction
Cells
Reactive Oxygen Species
Matrix Metalloproteinase 9
Catalase
Tumors
Intercellular Signaling Peptides and Proteins
Vascular Endothelial Growth Factor A
Cell Line
Microarrays
Superoxides
Hydrogen Peroxide
Superoxide Dismutase
Tumor Cell Line
Antioxidants
Genes
Enzymes
Proteins
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Hempel, Nadine ; Ye, Hanqing ; Abessi, Bryan ; Mian, Badar ; Melendez, J. Andres. / Altered redox status accompanies progression to metastatic human bladder cancer. In: Free Radical Biology and Medicine. 2009 ; Vol. 46, No. 1. pp. 42-50.
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Altered redox status accompanies progression to metastatic human bladder cancer. / Hempel, Nadine; Ye, Hanqing; Abessi, Bryan; Mian, Badar; Melendez, J. Andres.

In: Free Radical Biology and Medicine, Vol. 46, No. 1, 01.01.2009, p. 42-50.

Research output: Contribution to journalArticle

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