ArticleNeoplasia (New York, N.Y.)2017
Stromal PDGFR-α Activation Enhances Matrix Stiffness, Impedes Mammary Ductal Development, and Accelerates Tumor Growth.
Article in Neoplasia (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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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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
38 citing papers in PubMed, 67 citations in OpenAlex.
- Clinical utilities of platelet-derived growth factor signaling in breast cancer.Pharmacological research · 2026Review
- Review
- Contractile fibroblasts form a transient niche for the branching mammary epithelium.Nature communications · 2025Article
- Article
- Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.Experimental hematology & oncology · 2025Review
- A Modular, Cost-Effective, and Pumpless Perfusion Assembly for the Long-Term Culture of Engineered Microvessels.Micromachines · 2025Article
- Mechanomemory of pulmonary fibroblasts demonstrates reversibility of transcriptomics and contraction phenotypes.Biomaterials · 2025Article
- Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease.Biomolecules · 2024Review
- Linking cell mechanical memory and cancer metastasis.Nature reviews. Cancer · 2024Review
- Chondroitin sulfate, dermatan sulfate, and hyaluronic acid differentially modify the biophysical properties of collagen-based hydrogels.Acta biomaterialia · 2024Article
- Primary cilia-associated signalling in squamous cell carcinoma of head and neck region.Frontiers in oncology · 2024Review
- Fibroblast-induced mammary epithelial branching depends on fibroblast contractility.PLoS biology · 2024Article
- Multiple aspects of matrix stiffness in cancer progression.Frontiers in oncology · 2024Review
- Fibroblast-Epithelium Co-culture Methods Using Epithelial Organoids and Cell Line-Derived Spheroids.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Stiffness-induced cancer-associated fibroblasts are responsible for immunosuppression in a platelet-derived growth factor ligand-dependent manner.PNAS nexus · 2023Article
- Extracellular Matrix-Derived Biophysical Cues Mediate Interstitial Flow-Induced Sprouting Angiogenesis.ACS applied materials & interfaces · 2023Article
- Long-chain noncoding RNA sequencing analysis reveals the molecular profiles of chemically induced mammary epithelial cells.Frontiers in genetics · 2023Article
- Chemical Effects on Breast Development, Function, and Cancer Risk: Existing Knowledge and New Opportunities.Current environmental health reports · 2022Review
- Article
- Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
The extracellular matrix (ECM) is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα) specifically in the stroma. Hyperactivation of PDGFRα in the mammary stroma severely hindered pubertal mammary ductal morphogenesis, but did not interrupt the lobuloalveolar differentiation program. Increased stromal PDGFRα signaling induced mammary fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid (HA) and collagen deposition. Mammary fibroblasts with PDGFRα hyperactivation also decreased hydraulic permeability of a collagen substrate in an in vitro microfluidic device assay, which was mitigated by inhibition of either PDGFRα or HA. Fibrosis seen in this model significantly increased the overall stiffness of the mammary gland as measured by atomic force microscopy. Further, mammary tumor cells injected orthotopically in the fat pads of mice with stromal activation of PDGFRα grew larger tumors compared to controls. Taken together, our data establish that aberrant stromal PDGFRα signaling disrupts ECM homeostasis during mammary gland development, resulting in increased mammary stiffness and increased potential for tumor growth.
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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 Socratic graph.