ArticleCancer research2012
CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that regulates breast cancer stem cells.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers.
What it found
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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.
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Who cites it
245 citing papers in PubMed, 401 citations in OpenAlex.
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
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- Scalable longitudinal imaging and transcriptomics of cells in dynamic enclosures.bioRxiv : the preprint server for biology · 2026Article
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- Chemokine-chemokine receptor axis: Emerging immunotherapeutic paradigms for solid tumor microenvironment reprogramming.Chinese medical journal · 2026Review
- Preferential crosstalk between perifollicular capillary vessels and dermal papilla cells during hair cycling homeostasis.Scientific reports · 2026Article
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- "Cytokine-Mediated tumor sensitization: mechanistic frameworks and therapeutic opportunities in cancer Immunotherapy".Clinical and experimental medicine · 2026Review
- Increased Toll-Like Receptor-4 Signalling in Breast Tissue of High Fibroglandular Density.Journal of mammary gland biology and neoplasia · 2026Article
- CCL2/CCR2 signaling pathway in tumorigenesis and metastasis (Review).Oncology letters · 2025Review
- Trained Immunity in Health and Disease.MedComm · 2025Review
- Cancer Cell-Secreted miR-33a Reduces Stress Granule Formation by Targeting Polyamine Metabolism in Stroma to Promote Tumourigenesis.Journal of extracellular vesicles · 2025Article
- IL-6 predicts CDK4/6 inhibitor resistance, identifying STAT3 as a target in HR + /HER2-negative metastatic breast cancer.NPJ precision oncology · 2025Article
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- The Autophagy Inhibitor Bafilomycin Inhibits Antibody-Dependent Natural Killer Cell-Mediated Killing of Breast Carcinoma Cells.International journal of molecular sciences · 2025Article
- Obesity-cancer axis crosstalk: Molecular insights and therapeutic approaches.Acta pharmaceutica Sinica. B · 2025Review
- CCL2 blockade combined with PD-1/P-selectin immunomodulators impedes breast cancer brain metastasis.Brain : a journal of neurology · 2025Article
- Tumor microenvironment as niche constructed by cancer stem cells: Breaking the ecosystem to combat cancer.Journal of advanced research · 2025Review
- Article
- State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
185 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Cancer stem cells (CSC) play critical roles in cancer initiation, progression, and therapeutic refractoriness. Although many studies have focused on the genes and pathways involved in stemness, characterization of the factors in the tumor microenvironment that regulate CSCs is lacking. In this study, we investigated the effects of stromal fibroblasts on breast cancer stem cells. We found that compared with normal fibroblasts, primary cancer-associated fibroblasts (CAF) and fibroblasts activated by cocultured breast cancer cells produce higher levels of chemokine (C-C motif) ligand 2 (CCL2), which stimulates the stem cell-specific, sphere-forming phenotype in breast cancer cells and CSC self-renewal. Increased CCL2 expression in activated fibroblasts required STAT3 activation by diverse breast cancer-secreted cytokines, and in turn, induced NOTCH1 expression and the CSC features in breast cancer cells, constituting a cancer-stroma-cancer signaling circuit. In a xenograft model of paired fibroblasts and breast cancer tumor cells, loss of CCL2 significantly inhibited tumorigenesis and NOTCH1 expression. In addition, upregulation of both NOTCH1 and CCL2 was associated with poor differentiation in primary breast cancers, further supporting the observation that NOTCH1 is regulated by CCL2. Our findings therefore suggest that CCL2 represents a potential therapeutic target that can block the cancer-host communication that prompts CSC-mediated disease progression.
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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.