ArticleOncotarget2013
Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials.European journal of cancer (Oxford, England : 1990) · 2016Pooled it
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- Analysis of neuroglia and immune cells in the tumor microenvironment of breast cancer brain metastasis.Cancer biology & therapy · 2024Review
- Tissue-Resident Macrophages in Cancer: Friend or Foe?Cancer medicine · 2024Review
- Organotypic 3D Ex Vivo Co-culture Model of the Macro-metastasis/Organ Parenchyma Interface.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Antitumor Therapy Targeting the Tumor Microenvironment.Journal of oncology · 2023Review
- Article
- Circulating inflammatory cells in patients with metastatic breast cancer: Implications for treatment.Frontiers in oncology · 2022Review
- Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.Frontiers in oncology · 2022Review
- The tumor microenvironment as driver of stemness and therapeutic resistance in breast cancer: New challenges and therapeutic opportunities.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Zoledronic acid inhibits the growth of cancer stem cell derived from cervical cancer cell by attenuating their stemness phenotype and inducing apoptosis and cell cycle arrest through the Erk1/2 and Akt pathways.Journal of experimental & clinical cancer research : CR · 2019Article
- The Evolving Landscape of Brain Metastasis.Trends in cancer · 2018Review
- Article
- Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts.Oncotarget · 2017Article
- Pro-Tumoral Inflammatory Myeloid Cells as Emerging Therapeutic Targets.International journal of molecular sciences · 2016Review
- [Tumor Cells and Micro-environment in Brain Metastases].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether thisis due to directtoxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis.
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Registered trials
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.