ArticleBiochimica et biophysica acta2015
Regulation of MMP-1 expression in response to hypoxia is dependent on the intracellular redox status of metastatic bladder cancer cells.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 74 citations in OpenAlex.
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- The Dual Role of Dietary Phytochemicals in Oxidative Stress: Implications for Oncogenesis, Cancer Chemoprevention, and ncRNA Regulation.Antioxidants (Basel, Switzerland) · 2025Review
- Reactive Oxygen Species: From Tumorigenesis to Therapeutic Strategies in Cancer.Cancer medicine · 2025Review
- Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation.Archives of pharmacal research · 2025Review
- Hypoxia alters the response of ovarian cancer cells to the mitomycin C drug.Frontiers in cell and developmental biology · 2025Article
- Edaravone: A Novel Possible Drug for Cancer Treatment?International journal of molecular sciences · 2024Review
- Butein Increases Resistance to Oxidative Stress and Lifespan with Positive Effects on the Risk of Age-Related Diseases inAntioxidants (Basel, Switzerland) · 2024Article
- Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.Frontiers in oncology · 2024Review
- Association ofHealth science reports · 2023Article
- Matrix Metalloproteinases Inhibitors in Cancer Treatment: An Updated Review (2013-2023).Molecules (Basel, Switzerland) · 2023Review
- Effects of Fisetin, a Plant-Derived Flavonoid, on Response to Oxidative Stress, Aging, and Age-Related Diseases inPharmaceuticals (Basel, Switzerland) · 2022Article
- STEAP3 can predict the prognosis and shape the tumor microenvironment of clear cell renal cell carcinoma.BMC cancer · 2022Article
- Cancer-derived extracellular succinate: a driver of cancer metastasis.Journal of biomedical science · 2022Review
- Mitochondrial trafficking and redox/phosphorylation signaling supporting cell migration phenotypes.Frontiers in molecular biosciences · 2022Review
- Post-amputation reactive oxygen species production is necessary for axolotls limb regeneration.Frontiers in cell and developmental biology · 2022Article
- A vicious circle in breast cancer: The interplay between inflammation, reactive oxygen species, and microRNAs.Frontiers in oncology · 2022Review
- Interstitial collagenase MMP-1 and EMMPRIN in cell lines and in clinical specimens of cervical squamous cell carcinoma.Molecular biology reports · 2021Article
- The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression.Cells · 2021Review
- mRNA Expression Analysis of E-Cadherin, VEGF, and MMPs in Gastric Cancer: a Pilot Study.Indian journal of surgical oncology · 2021Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
High steady-state reactive oxygen species (ROS) production has been implicated with metastatic disease progression. We provide new evidence that this increased intracellular ROS milieu uniquely predisposes metastatic tumor cells to hypoxia-mediated regulation of the matrix metalloproteinase MMP-1. Using a cell culture metastatic progression model we previously reported that steady-state intracellular H2O2 levels are elevated in highly metastatic 253J-BV bladder cancer cells compared to their non-metastatic 253J parental cells. 253J-BV cells display higher basal MMP-1 expression, which is further enhanced under hypoxic conditions (1% O2). This hypoxia-mediated MMP-1 increase was not observed in the non-metastatic 253J cells. Hypoxia-induced MMP-1 increases are accompanied by the stabilization of hypoxia-inducible transcription factors (HIFs)-1α and HIF-2α, and a rise in intracellular ROS in metastatic 253J-BV cells. RNA interference studies show that hypoxia-mediated MMP-1 expression is primarily dependent on the presence of HIF-2α. Further, hypoxia promotes migration and spheroid outgrowth of only the metastatic 253J-BV cells and not the parental 253J cells. The observed HIF stabilization, MMP-1 expression and migration under hypoxia are dependent on increases in intracellular ROS, as these effects are attenuated by treatment with the antioxidant N-acetyl-L-cysteine. These data show that ROS play an important role in hypoxia-mediated MMP-1 expression and that an elevated intracellular redox environment, as observed in metastasis, predisposes tumor cells to an enhanced hypoxic response. It further supports the notion that metastatic tumor cells are uniquely able to utilize intracellular increases in ROS to drive pro-metastatic signaling events and highlights the important interplay between ROS and hypoxia in malignancy.
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