ArticleBMC cancer2010
Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4.
Article in BMC cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- The potential of hypoxia markers as target for breast molecular imaging--a systematic review and meta-analysis of human marker expression.BMC cancer · 2013Pooled it
- Assessment of the Targeted Therapeutic Potential of Naringenin-Benzyl Piperazine Derivatives on Hypoxia-Induced JAK/STAT Pathway in Breast and Ovarian Cancers.Archiv der Pharmazie · 2026Article
- Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1.European journal of histochemistry : EJH · 2021Article
- The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature.International journal of molecular sciences · 2021Review
- The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension.APL bioengineering · 2020Article
- Targeting the phosphoinositide 3-kinase/AKT pathways by small molecules and natural compounds as a therapeutic approach for breast cancer cells.Molecular biology reports · 2019Article
- Randomly Distributed K14Cancer research · 2019Article
- Curcumin Suppresses Hepatic Stellate Cell-Induced Hepatocarcinoma Angiogenesis and Invasion through Downregulating CTGF.Oxidative medicine and cellular longevity · 2019Article
- GPCR Modulation in Breast Cancer.International journal of molecular sciences · 2018Review
- CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- The Different Routes to Metastasis via Hypoxia-Regulated Programs.Trends in cell biology · 2018Review
- Hypoxia‑induced expression of CXCR4 favors trophoblast cell migration and invasion via the activation of HIF‑1α.International journal of molecular medicine · 2018Article
- BK channels blockage inhibits hypoxia-induced migration and chemoresistance to cisplatin in human glioblastoma cells.Journal of cellular physiology · 2018Article
- High co-expression of the SDF1/CXCR4 axis in hepatocarcinoma cells is regulated by AnnexinA7 in vitro and in vivo.Cell communication and signaling : CCS · 2018Article
- Inhibitors of HIF-1α and CXCR4 Mitigate the Development of Radiation Necrosis in Mouse Brain.International journal of radiation oncology, biology, physics · 2018Article
- Hypoxia-induced reactive oxygen species mediate N-cadherin and SERPINE1 expression, EGFR signalling and motility in MDA-MB-468 breast cancer cells.Scientific reports · 2017Article
- Resveratrol inhibits hepatocellular carcinoma progression driven by hepatic stellate cells by targeting Gli-1.Molecular and cellular biochemistry · 2017Article
- Stromal cell derived factor-1, CXCR4 and CXCR7 gene transcripts in pterygia.Journal of current ophthalmology · 2017Article
- PML promotes metastasis of triple-negative breast cancer through transcriptional regulation of HIF1A target genes.JCI insight · 2017Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemokine SDF1alpha and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1alpha.
methodsThree breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability.
resultsCXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-alpha in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness.
conclusionsCXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.
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