ArticleThe Journal of clinical investigation2009
Prevention of hypoxia by myoglobin expression in human tumor cells promotes differentiation and inhibits metastasis.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 74 citations in OpenAlex.
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- Pro-Apoptotic and Anti-Invasive Properties Underscore the Tumor-Suppressing Impact of Myoglobin on a Subset of Human Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Myoglobin expression by alternative transcript in different mesenchymal stem cells compartments.Stem cell research & therapy · 2022Article
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- Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties.Frontiers in endocrinology · 2021Article
- Expression of Myoglobin in Normal and Cancer Brain Tissues: Correlation With Hypoxia Markers.Frontiers in oncology · 2021Article
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- Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport.Redox biology · 2020Review
- Pancreatic cancer stroma: an update on therapeutic targeting strategies.Nature reviews. Gastroenterology & hepatology · 2020Review
- Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation.iScience · 2020Article
- The role of myoglobin in epithelial cancers: Insights from transcriptomics.International journal of molecular medicine · 2020Article
- Increased levels of the long noncoding RNA, HOXA-AS3, promote proliferation of A549 cells.Cell death & disease · 2018Article
- Influence of hypoxia-related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF.Oncology letters · 2018Article
- Alternative scheduling of pulsatile, high dose sunitinib efficiently suppresses tumor growth.Journal of experimental & clinical cancer research : CR · 2016Article
- Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue.Nature communications · 2015Article
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5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a tumor grows, it requires increased amounts of oxygen. However, the tumor blood vessels that form to meet this demand are functionally impaired, leading to regions of hypoxia within the tumor. Such hypoxia is one of the hallmarks of malignancy and is thought to promote a number of tumorigenic properties. Here, we sought to determine how tumors without hypoxia would progress by engineering A549 human lung carcinoma cells to ectopically express myoglobin (Mb), a multifunctional heme protein that specializes in oxygen transport, storage, and buffering. Mb expression prevented the hypoxic response in vitro and delayed tumor engraftment and reduced tumor growth following xenotransplantation into mice. Experimental tumors expressing Mb displayed reduced or no hypoxia, minimal HIF-1alpha levels, and a homogeneously low vessel density. Mb-mediated tumor oxygenation promoted differentiation of cancer cells and suppressed both local and distal metastatic spreading. These effects were primarily due to reduced tumor hypoxia, because they were not observed using point-mutated forms of myoglobin unable to bind oxygen and they were abrogated by expression of a constitutively active form of HIF-1alpha. Although limited to xenograft models, these data provide experimental proof of the concept that hypoxia is not just a side effect of deregulated growth but a key factor on which the tumor relies in order to promote its own expansion.
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