ArticleScientific reports2023
Primary breast tumor induced extracellular matrix remodeling in premetastatic lungs.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 33 citations in OpenAlex.
- Niches in cancer: from primary tumors to metastatic disease.Journal of hematology & oncology · 2026Review
- Review
- T cells are critical for pre-metastatic niche formation through the STAT3/IL-17 axis.Journal for immunotherapy of cancer · 2026Article
- A guide to the types, structures, and multifaceted functions of matrix metalloproteinases in cancer.The FEBS journal · 2026Review
- Integrative transcriptomic analysis reveals novel targets for personalized medicine across seven metastatic breast cancer subtypes.Scientific reports · 2026Article
- RESCUE: recovery of unattributed expression patterns in spatial transcriptomics.Nature communications · 2026Article
- The Emerging Role of Mechanobiology in Connecting Metabolic and Cardiovascular Diseases: From Fundamentals to Future Therapies.Biomedicines · 2026Review
- The unseen architects of metastasis: coagulation factors in pre-metastatic niche development.Cell communication and signaling : CCS · 2026Review
- Micro-Organ Chip Deciphers Tumor-Derived G-CSF as Remote Commander of Lung Pre-Metastatic Niche via VEGFA-KDR Cascade.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineering Complex Breast Tumor-Stroma Models: TMPyP4-Photodynamic Therapy Is More Effective at the Metastatic Site in Breast Tumors.ACS biomaterials science & engineering · 2026Article
- A label-free microLC-SWATH-MS methodology with immunoaffinity depletion of highly abundant serum proteins for quantitative proteomic comparison of fresh-frozen human normal breast tissue and tumor clinical specimens.Frontiers in molecular biosciences · 2026Article
- Article
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
- Enhanced Collagen Prolyl 4-Hydroxylase Activity and Expression Promote Cancer Progression via Both Canonical and Non-Canonical Mechanisms.International journal of molecular sciences · 2025Review
- Unveiling Matrix Metalloproteinase 13's Dynamic Role in Breast Cancer: A Link to Physical Changes and Prognostic Modulation.International journal of molecular sciences · 2025Review
- Forcing the code: tension modulates signaling to drive morphogenesis and malignancy.Genes & development · 2025Review
- Serum EMMPRIN/CD147 promotes the lung pre-metastatic niche in a D2A1 mammary carcinoma mouse model.Frontiers in immunology · 2025Article
- Premetastatic niche mechanics and organotropism in breast cancer.npj biological physics and mechanics · 2025Review
- Potential target within the tumor microenvironment - MT1-MMP.Frontiers in immunology · 2025Review
- Editorial: Interaction of cell subtypes in tumor microenvironment, and implications for immunotherapy.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The premetastatic niche hypothesis proposes an active priming of the metastatic site by factors secreted from the primary tumor prior to the arrival of the first cancer cells. We investigated several extracellular matrix (ECM) structural proteins, ECM degrading enzymes, and ECM processing proteins involved in the ECM remodeling of the premetastatic niche. Our in vitro model consisted of lung fibroblasts, which were exposed to factors secreted by nonmalignant breast epithelial cells, nonmetastatic breast cancer cells, or metastatic breast cancer cells. We assessed ECM remodeling in vivo in premetastatic lungs of female mice growing orthotopic primary breast tumor xenografts, as compared to lungs of control mice without tumors. Premetastatic lungs contained significantly upregulated Collagen (Col) Col4A5, matrix metalloproteinases (MMPs) MMP9 and MMP14, and decreased levels of MMP13 and lysyl oxidase (LOX) as compared to control lungs. These in vivo findings were consistent with several of our in vitro cell culture findings, which showed elevated Col14A1, Col4A5, glypican-1 (GPC1) and decreased Col5A1 and Col15A1 for ECM structural proteins, increased MMP2, MMP3, and MMP14 for ECM degrading enzymes, and decreased LOX, LOXL2, and prolyl 4-hydroxylase alpha-1 (P4HA1) for ECM processing proteins in lung fibroblasts conditioned with metastatic breast cancer cell media as compared to control. Taken together, our data show that premetastatic priming of lungs by primary breast tumors resulted in significant ECM remodeling which could facilitate metastasis by increasing interstitial fibrillar collagens and ECM stiffness (Col14A1), disruptions of basement membranes (Col4A5), and formation of leaky blood vessels (MMP2, MMP3, MMP9, and MMP14) to promote metastasis.
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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.