ArticleNature2014
Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 445 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
445 citing papers in PubMed, 1 synthesis or guideline pooled it, 661 citations in OpenAlex.
- Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Myeloid-derived suppressor cells in cancer: biology, regulatory networks and theranostic prospects.Signal transduction and targeted therapy · 2026Review
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- Unveiling the Paradoxical Tumor-Suppressive Role of CCL2/CCR2 in Bladder Cancer: A Novel Immunotherapeutic Strategy.Cancers · 2026Article
- Tumor-Associated Macrophages (TAMs) in Cancer: Functional Programs, Metastatic Mechanisms, and Therapeutic Targeting.Cancers · 2026Review
- Macrophage plasticity in the osteosarcoma tumor microenvironment: opportunities and challenges for immunotherapy.Journal of cancer research and clinical oncology · 2026Review
- ATM promotes bone metastatic propensity of breast cancer by inducing osteoclastogenesis via the NFκB-CCL2 pathway.Acta pharmacologica Sinica · 2026Article
- Macrophages: Targets for next-generation cancer immunotherapy.Cancer cell · 2026Review
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- HOXA10 drives immune evasion in early lung adenocarcinoma by recruiting immunosuppressive macrophages via NF-κB/CCL2 signaling.Journal of experimental & clinical cancer research : CR · 2026Article
- Tumor-Associated Macrophages as Therapeutic Targets: Deciphering Interaction Networks and Advancing Clinical Translation.MedComm · 2026Review
- Monocyte-Macrophage Lineages in Cancer: Biology, Plasticity, and Therapeutic Targeting.Cancer biome and targeted therapy · 2026Article
- Transmembrane lectins in cancer immunity: emerging drivers of myeloid-mediated immunosuppression.Frontiers in immunology · 2026Review
- Immunity and Beyond: Emerging Roles of Monocytes and Macrophages in Cancer.Advances in experimental medicine and biology · 2026Review
- Spiegelmer Aptamers: Innovative Approach in Breast Cancer.Breast cancer : basic and clinical research · 2026Review
- Spatial Fibroblast-Macrophage Niches in Gastric Cancer: Mechanisms of Immune Exclusion, Therapeutic Resistance, and Targeted Intervention.OncoTargets and therapy · 2026Review
- The CCL2-CCR2 axis in primary lung cancer and pulmonary metastasis: from molecular mechanisms to therapeutic potentials.Frontiers in immunology · 2026Review
- Mechanoresponsive reprogramming of tumor-associated macrophages during cancer progression.Frontiers in cell and developmental biology · 2026Review
385 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Secretion of C-C chemokine ligand 2 (CCL2) by mammary tumours recruits CCR2-expressing inflammatory monocytes to primary tumours and metastatic sites, and CCL2 neutralization in mice inhibits metastasis by retaining monocytes in the bone marrow. Here we report a paradoxical effect of CCL2 in four syngeneic mouse models of metastatic breast cancer. Surprisingly, interruption of CCL2 inhibition leads to an overshoot of metastases and accelerates death. This is the result of monocyte release from the bone marrow and enhancement of cancer cell mobilization from the primary tumour, as well as blood vessel formation and increased proliferation of metastatic cells in the lungs in an interleukin (IL)-6- and vascular endothelial growth factor (VEGF)-A-dependent manner. Notably, inhibition of CCL2 and IL-6 markedly reduced metastases and increased survival of the animals. CCL2 has been implicated in various neoplasias and adopted as a therapeutic target. However, our results call for caution when considering anti-CCL2 agents as monotherapy in metastatic disease and highlight the tumour microenvironment as a critical determinant of successful anti-metastatic therapy.
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What OpenQuestion holds
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.