ArticleProceedings of the National Academy of Sciences of the United States of America2003
Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 169 papers, 1 of them a synthesis 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.
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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
169 citing papers in PubMed, 1 synthesis or guideline pooled it, 480 citations in OpenAlex.
- Pooled it
- Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC.Cancer biomarkers : section A of Disease markers · 2017Trial
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- An update on the landscape of collagen bioactive fragments.The FEBS journal · 2026Review
- Testing cellular provenance in the cancer extracellular matrix.Frontiers in cell and developmental biology · 2026Review
- Type IV collagen derived non-collagenous domain α6 (IV) NC1 and its derivative fragments inhibit endothelial cell proliferation and attenuatesCytotechnology · 2025Article
- Developments in Extracellular Matrix-Based Angiogenesis Therapy for Ischemic Heart Disease: A Review of Current Strategies, Methodologies and Future Directions.Biotech (Basel (Switzerland)) · 2025Review
- Lung cancer: Animal model of lung cancer, molecular carcinogenesis of lung cancer, and antitumor effect ofOpen veterinary journal · 2025Review
- The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen.International journal of molecular sciences · 2024Review
- A Review of the Use of Native and Engineered Probiotics for Colorectal Cancer Therapy.International journal of molecular sciences · 2024Review
- Homeostatic Regulation of Pro-Angiogenic and Anti-Angiogenic Proteins via Hedgehog, Notch Grid, and Ephrin Signaling in Tibial Dyschondroplasia.Animals : an open access journal from MDPI · 2023Review
- Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes.Nature communications · 2023Article
- Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Weaving the nest: extracellular matrix roles in pre-metastatic niche formation.Frontiers in oncology · 2023Review
- 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
- Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer.International journal of molecular sciences · 2022Review
- The Angiogenic Balance and Its Implications in Cancer and Cardiovascular Diseases: An Overview.Medicina (Kaunas, Lithuania) · 2022Review
- An overview of resistance to chemotherapy in osteosarcoma and future perspectives.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Endostatin in fibrosis and as a potential candidate of anti-fibrotic therapy.Drug delivery · 2021Review
109 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tumstatin and endostatin are two inhibitors of angiogenesis derived from precursor human collagen molecules known as alpha 3 chain of type IV collagen and alpha1 chain of type XVIII collagen, respectively. Although both these inhibitors are noncollagenous (NC1) domain fragments of collagens, they only share a 14% amino acid homology. In the present study we evaluated the functional receptors, mechanism of action, and intracellular signaling induced by these two collagen-derived inhibitors. Human tumstatin prevents angiogenesis via inhibition of endothelial cell proliferation and promotion of apoptosis with no effect on migration, whereas human endostatin prevents endothelial cell migration with no effect on proliferation. We demonstrate that human tumstatin binds to alpha v beta 3 integrin in a vitronectin/fibronectin/RGD cyclic peptide independent manner, whereas human endostatin competes with fibronectin/RGD cyclic peptide to bind alpha 5 beta 1 integrin. The activity of human tumstatin is mediated by alpha v beta 3 integrin, whereas the activity of human endostatin is mediated by alpha 5 beta 1 integrin. Additionally, although human tumstatin binding to alpha v beta 3 integrin leads to the inhibition of Cap-dependent translation (protein synthesis) mediated by focal adhesion kinase/phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 pathway, human endostatin binding to alpha 5 beta 1 integrin leads to the inhibition of focal adhesion kinase/c-Raf/MEK1/2/p38/ERK1 mitogen-activated protein kinase pathway, with no effect on phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 and Cap-dependent translation. Collectively, such distinct properties of human tumstatin and human endostatin provide the first insight into their diverse antiangiogenic actions and argue for combining them for targeting tumor angiogenesis.
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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.