ArticleIntegrative biology : quantitative biosciences from nano to macro2015
Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.
Article in Integrative biology : quantitative biosciences from nano to macro, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 624 papers.
What it found
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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
624 citing papers in PubMed, 1,059 citations in OpenAlex.
- Tumor Biomechanics Quantified Using MR Elastography to Predict Response to Neoadjuvant Chemotherapy in Individuals with Breast Cancer.Radiology. Imaging cancer · 2025Trial
- Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial.Breast cancer research : BCR · 2024Trial
- Reprogramming tumor-associated macrophages in breast cancer: from myeloid plasticity and tumor-promoting programs to CAR-macrophage therapy.Journal of hematology & oncology · 2026Review
- Mechanical memory as a metastatic compass: a comparative framework for understanding organotropism through biophysical priming.Cancer metastasis reviews · 2026Review
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Microfluidic perspectives on chimeric antigen receptor T-cell migration in solid tumours: highlighting physical confinement as a key barrier.Molecular systems design & engineering · 2026Review
- Exploring shear-wave elastography and apparent diffusion coefficient in breast lesion characterization: diagnostic accuracy and inter-modality correlation.La Radiologia medica · 2026Article
- Nanoscale-Sensitive VSFG Microscopy for Identifying Breast Tumor in FFPE Samples.Chemical & biomedical imaging · 2026Article
- Article
- Sono-Mechanogenetics: Linking Ultrasound Physics With Cellular Mechanobiology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Elevation of liver elasticity following radiofrequency ablation reflects neutrophil-mediated abscopal effect in liver cancer.JHEP reports : innovation in hepatology · 2026Article
- Single-Cell RNA-Seq Combined With Bulk RNA-Seq Revealed the Involvement of Pancreatic Cancer Tissue-Resident Macrophages in Tumour Progression and the Immunotherapy Response.Journal of cellular and molecular medicine · 2026Article
- Non-linear Characterization of Commercial and Decellularized Hydrogels: Statistical Framework Enhanced by Bayesian Optimization.Cellular and molecular bioengineering · 2026Article
- Diagnostic performance of multimodal ultrasonography for molecular subtyping of breast cancer: a retrospective study.Gland surgery · 2026Article
- Integrated Collagen Architecture and Composition Improve Risk Stratification in Triple-Negative Breast Cancer.bioRxiv : the preprint server for biology · 2026Article
- Review
- Exosomal MicroRNAs as Drivers of Desmoplasia and Treatment Resistance in Breast Cancer: Mechanisms, Biomarker Potential, and Therapeutic Opportunities.Biomolecules · 2026Review
- Common Signatures of Altered Gene Regulation and Invasiveness of Different Breast Cancer Cell Lines after Matrix Interface Crossing.Advanced healthcare materials · 2026Article
- Nuclear Mechanotransduction Across the Metastatic Cascade: Decoding Spatiotemporal Heterogeneity in Cancer Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Metastasis on pause: How dormant tumor cells stay hidden within the tumor microenvironment and evade immune surveillance.Molecular oncology · 2026Review
564 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta.
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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.