ArticleProceedings of the National Academy of Sciences of the United States of America2000
Elevated matrix metalloprotease and angiostatin levels in integrin alpha 1 knockout mice cause reduced tumor vascularization.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 396 citations in OpenAlex.
- JMJD6-driven epigenetic activation of COL4A2 reprograms glioblastoma vascularization via integrin α1β1-dependent PI3K/MAPK signaling.Acta neuropathologica communications · 2025Article
- Gene therapy in neovascular age related macular degeneration: an update.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Review
- Tumor microenvironment and immunotherapy: from bench to bedside.Medical oncology (Northwood, London, England) · 2025Review
- RETRACTED: Structure-Activity Relationship of Synthetic Linear KTS-Peptides Containing Meta-Aminobenzoic Acid as Antagonists of α1β1 Integrin with Anti-Angiogenic and Melanoma Anti-Tumor Activities.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Extracellular matrix remodelling in obesity and metabolic disorders.Life metabolism · 2023Article
- Weaving the nest: extracellular matrix roles in pre-metastatic niche formation.Frontiers in oncology · 2023Review
- The effects of inhibition and siRNA knockdown of collagen-binding integrins on human umbilical vein endothelial cell migration and tube formation.Scientific reports · 2022Article
- The roles of metabolic profiles and intracellular signaling pathways of tumor microenvironment cells in angiogenesis of solid tumors.Cell communication and signaling : CCS · 2022Review
- Involvement of the extracellular matrix and integrin signalling proteins in skeletal muscle glucose uptake.The Journal of physiology · 2022Review
- RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis.The EMBO journal · 2021Article
- Selectivity of the collagen-binding integrin inhibitors, TC-I-15 and obtustatin.Toxicology and applied pharmacology · 2021Article
- Overexpression of Msx1 in Mouse Lung Leads to Loss of Pulmonary Vessels Following Vascular Hypoxic Injury.Cells · 2021Article
- iTRAQ-based quantitative proteomic analysis of thoracic aortas from adult rats born to preeclamptic dams.Clinical proteomics · 2021Article
- Review of Integrin-Targeting Biomaterials in Tissue Engineering.Advanced healthcare materials · 2020Review
- Prostate cancer-derived MMP-3 controls intrinsic cell growth and extrinsic angiogenesis.Neoplasia (New York, N.Y.) · 2020Article
- Histone Acetyltransferase p300 Inhibitor Improves Coronary Flow Reserve in SIRT3 (Sirtuin 3) Knockout Mice.Journal of the American Heart Association · 2020Article
- Influence of the integrin alpha-1 subunit and its relationship with high-fat diet upon extracellular matrix synthesis in skeletal muscle and tendon.Cell and tissue research · 2020Article
- Identification of putative biomarkers for Infantile Hemangiomas and Propranolol treatment via data integration.Scientific reports · 2020Article
- Reciprocal Interplay Between Fibrillar Collagens and Collagen-Binding Integrins: Implications in Cancer Progression and Metastasis.Frontiers in oncology · 2020Review
- The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model.Investigational new drugs · 2019Article
81 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrin alpha1beta1 is a collagen receptor abundantly expressed on microvascular endothelial cells. As well as being the only collagen receptor able to activate the Ras/Shc/mitogen-activated protein kinase pathway promoting fibroblast cell proliferation, it also acts to inhibit collagen and metalloproteinase (MMP) synthesis. We have observed that in integrin alpha1-null mice synthesis of MMP7 and MMP9 was markedly increased compared with that of their wild-type counterparts. As MMP7 and MMP9 have been shown to generate angiostatin from circulating plasminogen, and angiostatin acts as a potent inhibitor of endothelial cell proliferation, we determined whether tumor vascularization was altered in the alpha1-null mice. Tumors implanted into alpha1-null mice showed markedly decreased vascularization, with a reduction in capillary number and size, which was accompanied by an increase in plasma levels of angiostatin due to the action of MMP7 and MMP9 on circulating plasminogen. In vitro analysis of alpha1-null endothelial cells revealed a marked reduction of their proliferation on both integrin alpha1-dependent (collagenous) and independent (noncollagenous) substrata. This reduction was prevented by culturing alpha1-null cells with plasma derived from plasminogen-null animals, thus omitting the source from which to generate angiostatin. Plasma from tumor-bearing alpha1-null animals uniquely inhibited endothelial cell growth, and this inhibition was relieved by the coaddition of either MMP inhibitors, or antibody to angiostatin. Integrin alpha1-deficient mice thus provide a genetically characterized model for enhanced angiostatin production and serve to reveal an unwanted potential side effect of MMP inhibition, increased tumor angiogenesis.
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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.