ArticleNature2009
Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis.
Article in Nature, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 613 papers, 2 of them syntheses 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
613 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,101 citations in OpenAlex.
- Mapping research trends in macrophage polarization and immunotherapeutic potential in prostate cancer: a bibliometric and visual analysis.Frontiers in oncology · 2026Pooled it
- Cutting edges and therapeutic opportunities on tumor-associated macrophages in lung cancer.Frontiers in immunology · 2022Pooled it
- Research advances on tumor-associated macrophages in pancreatic cancer.Biochemistry and biophysics reports · 2026Review
- T cells are critical for pre-metastatic niche formation through the STAT3/IL-17 axis.Journal for immunotherapy of cancer · 2026Article
- Astragalus-derived nano-agonist potentiates chemotherapy by reducing tumor-suppressive macrophages.Acta pharmaceutica Sinica. B · 2026Article
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Multimodal single-cell profiling reveals crosstalk between macrophages and stromal cells in poor prognostic cholangiocarcinoma patients.NPJ precision oncology · 2026Article
- The Role of Mean Platelet Volume (MPV) in Thyroid Cancers: A Scoping Review.Medicina (Kaunas, Lithuania) · 2026Review
- Macrophages Drive Ferroptosis Resistance after Radiotherapy.Cancer communications (London, England) · 2026Article
- From description to prediction: a multi-database bibliometric forecast-validation study of lung cancer and tumor-associated macrophages research (2005-2025).Frontiers in immunology · 2026Review
- The role of ECM-PIEZO1-axis-mediated mechanosensation in the central nervous system.Frontiers in neurology · 2026Review
- Enhancer-mediated NR2F2 recruitment activates BGN to promote tumor growth and shape tumor microenvironment in papillary thyroid cancer.Theranostics · 2026Article
- Dual-Action Theranostic Nanoparticles Delivering Toll-Like Receptor 2 Inhibitors and Chemotherapy Target Breast Cancer Cells and the Tumor Microenvironment.International journal of nanomedicine · 2026Article
- Sulfated Glycosaminoglycans in Inflammation.Advances in experimental medicine and biology · 2026Review
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- Plasma Fibronectin Drives Macrophage Elongation via Integrin β3-Tie2 Axis in Blood Clots.Cancers · 2025Article
- Enhancing anti-tumour immunity through modulating dendritic cell activation by combination therapy with a novel TLR2 agonist and PD-L1 Blockade.Journal of experimental & clinical cancer research : CR · 2025Article
- Phenotyping and clinical utility of phagocytic polyploid giant cancer macrophages in blood.Cancer letters · 2025Article
- Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications.Cancer cell · 2025Review
- Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.Journal of hematology & oncology · 2025Review
553 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Expression of concern
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Metastatic progression depends on genetic alterations intrinsic to cancer cells as well as the inflammatory microenvironment of advanced tumours. To understand how cancer cells affect the inflammatory microenvironment, we conducted a biochemical screen for macrophage-activating factors secreted by metastatic carcinomas. Here we show that, among the cell lines screened, Lewis lung carcinoma (LLC) were the most potent macrophage activators leading to production of interleukin-6 (IL-6) and tumour-necrosis factor-alpha (TNF-alpha) through activation of the Toll-like receptor (TLR) family members TLR2 and TLR6. Both TNF-alpha and TLR2 were found to be required for LLC metastasis. Biochemical purification of LLC-conditioned medium (LCM) led to identification of the extracellular matrix proteoglycan versican, which is upregulated in many human tumours including lung cancer, as a macrophage activator that acts through TLR2 and its co-receptors TLR6 and CD14. By activating TLR2:TLR6 complexes and inducing TNF-alpha secretion by myeloid cells, versican strongly enhances LLC metastatic growth. These results explain how advanced cancer cells usurp components of the host innate immune system, including bone-marrow-derived myeloid progenitors, to generate an inflammatory microenvironment hospitable for metastatic growth.
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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.