ArticleCancer cell2003
Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin.
Article in Cancer cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 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
207 citing papers in PubMed, 551 citations in OpenAlex.
- Proteolytic remodelling of the extracellular matrix by pericytes.The FEBS journal · 2026Review
- Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior.The FEBS journal · 2026Review
- Elevated serum soluble α3(IV)NC1 correlates with kidney injury and worse outcome in patients with anti-glomerular basement membrane disease.Frontiers in immunology · 2026Article
- GPR107: A key driver of breast cancer invasion and metastasis through collagen IV modulation.Cancer gene therapy · 2025Article
- 3D Bioprinting and Artificial Intelligence for Tumor Microenvironment Modeling: A Scoping Review of Models, Methods, and Integration Pathways.Molecular pharmaceutics · 2025Article
- Basement membranes in lung development, disease, and repair.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Beyond classical collagen: basement membrane collagen IV in age-associated lung diseases.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Serum matrix metalloproteinase-9 levels and enzymatic activity in patients with anti-glomerular basement membrane disease.Frontiers in medicine · 2025Article
- CDK4/6 inhibitors induce breast cancer senescence with enhanced anti-tumor immunogenic properties compared with DNA-damaging agents.Molecular oncology · 2024Article
- Circulating Podocalyxin, Tumstatin/Col-IVα3 and Chitinase 1: New Culprits in Vitiligo Occurrence.Dermatology practical & conceptual · 2024Article
- Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.Cancers · 2023Review
- Identification of unique α4 chain structure and conserved antiangiogenic activity of α3NC1 type IV collagen in zebrafish.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Immunotherapeutic Approaches for the Treatment of Glioblastoma Multiforme: Mechanism and Clinical Applications.International journal of molecular sciences · 2023Review
- Ectopic CH60 mediates HAPLN1-induced cell survival signaling in multiple myeloma.Life science alliance · 2023Article
- Opposing MMP-9 Expression in Mesenchymal Stromal Cells and Head and Neck Tumor Cells after Direct 2D and 3D Co-Culture.International journal of molecular sciences · 2023Article
- Bioactive extracellular matrix fragments in tendon repair.Cell and tissue research · 2022Review
- A Comparative Presentation of Mouse Models That Recapitulate Most Features of Alport Syndrome.Genes · 2022Review
- Tumor microenvironment and immunotherapy of oral cancer.European journal of medical research · 2022Review
- The effects of Juglone-Selenium combination on invasion and metastasis in pancreatic cancer cell lines.African health sciences · 2022Article
- MMP9: A Tough Target for Targeted Therapy for Cancer.Cancers · 2022Review
147 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We demonstrate a physiological role for tumstatin, a cleavage fragment of the alpha3 chain of type IV collagen (Col IValpha3), which is present in the circulation. Mice with a genetic deletion of Col IValpha3 show accelerated tumor growth associated with enhanced pathological angiogenesis, while angiogenesis associated with development and tissue repair are unaffected. Supplementing Col IValpha3-deficient mice with recombinant tumstatin to a normal physiological concentration abolishes the increased rate of tumor growth. The suppressive effects of tumstatin require alphaVbeta3 integrin expressed on pathological, but not on physiological, angiogenic blood vessels. Mice deficient in matrix metalloproteinase-9, which cleaves tumstatin efficiently from Col IValpha3, have decreased circulating tumstatin and accelerated growth of tumor. These results indicate that MMP-generated fragments of basement membrane collagen can have endogenous function as integrin-mediated suppressors of pathologic angiogenesis and 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 OpenQuestion graph.