ArticleCancers2021
Persistent Inflammatory Stimulation Drives the Conversion of MSCs to Inflammatory CAFs That Promote Pro-Metastatic Characteristics in Breast Cancer Cells.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 3 of them syntheses that pooled it.
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.
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
39 citing papers in PubMed, 3 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Collagenase-mediated extracellular matrix targeting for enhanced drug penetration and therapeutic efficacy in nanoscale delivery systems for cancer therapy.Journal of nanobiotechnology · 2025Pooled it
- Prognostic value of lymphocyte-to-monocyte ratio in patients with small cell lung cancer: a meta-analysis.World journal of surgical oncology · 2025Pooled it
- Pooled it
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- In vitro effects of tensile strain on cancer-associated and matched normal fibroblasts derived from oral squamous cell carcinoma: an exploratory study.BMC cancer · 2026Article
- PD-L1 and PD-L2 regulate in cell-autonomous and N-glycosylation-dependent manners the pro-tumorigenic characteristics and functions of human cancer-associated fibroblasts.Molecular medicine (Cambridge, Mass.) · 2026Article
- A Literature Review of Interleukins in the Development and Treatment of Breast Cancer.International journal of molecular sciences · 2026Review
- The Osteoimmunologic Basis of Biologic and Bioengineered Scaffolds in Fracture Healing.Bioengineering (Basel, Switzerland) · 2026Review
- Review
- Cancer-Associated Fibroblasts in the Treatment of Intrahepatic Cholangiocarcinoma: Present and Prospects.Journal of hepatocellular carcinoma · 2026Review
- Immune system, inflammatory response, and regulated cell death in breast cancer research (Review).Oncology reports · 2026Review
- Crosstalk between cancer‑associated fibroblasts and inflammation in tumor microenvironment: A novel perspective in cancer therapy (Review).Oncology reports · 2025Review
- Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis.Experimental hematology & oncology · 2025Review
- Article
- From Embryogenesis to Senescence: The Role of Mammary Gland Physiology in Breast Cancer Risk.Cancers · 2025Review
- Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.JCI insight · 2025Article
- Regulation of Cancer Stem Cells in the Tumor Microenvironment.Cancer heterogeneity and plasticity · 2025Article
- Unraveling the role of cancer-associated fibroblasts in colorectal cancer.World journal of gastrointestinal oncology · 2024Review
- Actin-related protein 2/3 complex subunit 1B promotes ovarian cancer progression by regulating the AKT/PI3K/mTOR signaling pathway.Journal of translational internal medicine · 2024Article
- The G Protein Estrogen Receptor (GPER) is involved in the resistance to the CDK4/6 inhibitor palbociclib in breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo conversion at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα + IL-1β (generally 14-18 days) gained a CAF-like morphology, accompanied by prominent changes in gene expression, including in stroma/fibroblast-related genes. These CAF-like cells expressed elevated levels of vimentin and fibroblast activation protein (FAP) and demonstrated significantly increased abilities to contract collagen gels. Moreover, they gained the phenotype of inflammatory CAFs, as indicated by the reduced expression of α smooth muscle actin (αSMA), increased proliferation, and elevated expression of inflammatory genes and proteins, primarily inflammatory chemokines. These inflammatory CAFs released factors that enhanced tumor cell dispersion, scattering, and migration; the inflammatory CAF-derived factors elevated cancer cell migration by stimulating the chemokine receptors CCR2, CCR5, and CXCR1/2 and Ras-activating receptors, expressed by the cancer cells. Together, these novel findings demonstrate that chronic inflammation can induce MSC-to-CAF conversion, leading to the generation of tumor-promoting inflammatory CAFs.
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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.