ArticlePLoS biology2012
Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 191 citations in OpenAlex.
- Differential Effects of Psychogenic Stress on Bone Morphology and Metabolism in Wistar Rats.Journal of bone metabolism · 2026Article
- TLR7 signature of tumour innervation reveals two distinct pathways of triple-negative breast cancer progression.British journal of cancer · 2026Article
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- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.International journal of molecular sciences · 2026Review
- Key role of the autonomic nervous system in breast cancer (Review).Experimental and therapeutic medicine · 2026Review
- Tyrosine hydroxylase as a therapeutic target: insights from adrenergic nerve and TNBC cell interactions.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Brain-cancer interactions outside the CNS.Oncogene · 2026Review
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- Comparing the Molecular Pharmacological Properties of Existing β-Blockers to Determine the Theoretically Most "Ideal" Anti-Cancer β-Blocker.Pharmacology research & perspectives · 2026Article
- From nerve to bone: a tale of autonomic nervous system, bone cells, and beyond.Military Medical Research · 2026Review
- PGD2/PTGDR2 Signaling Affects the Stemness of Gastric Cancer Stem Cells by Regulating Autophagy.Combinatorial chemistry & high throughput screening · 2026Article
- Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.Cancer communications (London, England) · 2026Review
- Chronic Restraint Stress Misaligns Corneal Clock via β-Adrenergic and Glucocorticoid Signaling, Altering Epithelial, Neural, Immune, Metabolic States.Investigative ophthalmology & visual science · 2025Article
- Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies.Military Medical Research · 2025Review
- Mesenchymal stroma drives axonogenesis and nerve-induced aggressiveness in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Hijacking of the nervous system in cancer: mechanism and therapeutic targets.Molecular cancer · 2025Review
- Bilosomal Co-Encapsulated Tamoxifen and Propranolol for Potentiated Anti-Breast Cancer Efficacy: In Vitro and In Vivo Investigation.Pharmaceutics · 2025Article
- Nerves at Play: The Peripheral Nervous System in Extracranial Malignancies.Cancer discovery · 2025Review
- Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells.Nature reviews. Cancer · 2024Review
67 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress) or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.