ArticlePeptides2011
An integrin-binding N-terminal peptide region of TIMP-2 retains potent angio-inhibitory and anti-tumorigenic activity in vivo.
Article in Peptides, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Immunomodulatory differences between mesenchymal stem cells from different oral tissues.Heliyon · 2024Article
- TIMP2 ameliorates blood-brain barrier disruption in traumatic brain injury by inhibiting Src-dependent VE-cadherin internalization.The Journal of clinical investigation · 2023Article
- The Continuing Saga of Tissue Inhibitor of Metalloproteinase 2: Emerging Roles in Tissue Homeostasis and Cancer Progression.The American journal of pathology · 2023Review
- Article
- Structure and computation-guided yeast surface display for the evolution of TIMP-based matrix metalloproteinase inhibitors.Frontiers in molecular biosciences · 2023Review
- Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability.International journal of molecular sciences · 2022Article
- Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer.Carcinogenesis · 2022Review
- Matrix Metalloproteinases MMP-2 and MMP-9, Their Inhibitors TIMP-1 and TIMP-2, Vascular Endothelial Growth Factor and sVEGFR-2 as Predictive Markers of Ischemic Retinopathy in Patients with Systemic Sclerosis-Case Series Report.International journal of molecular sciences · 2020Article
- Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer.Diagnostics (Basel, Switzerland) · 2020Review
- TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer.Carcinogenesis · 2020Article
- Reflections on the evolution of the vertebrate tissue inhibitors of metalloproteinases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Review
- Macromolecule-Network Electrostatics Controlling Delivery of the Biotherapeutic Cell Modulator TIMP-2.Biomacromolecules · 2018Article
- Effect of elastin-derived peptides on the production of tissue inhibitor of metalloproteinase-1, -2, and -3 and the ratios in various endothelial cell lines.Experimental and therapeutic medicine · 2015Article
- AP-1-Targeted Anti-Inflammatory Activities of the Nanostructured, Self-Assembling S5 Peptide.Mediators of inflammation · 2015Article
- The angiogenic asset of soft tissue sarcomas: a new tool to discover new therapeutic targets.Bioscience reports · 2014Review
- Molecular mechanisms of tissue inhibitor of metalloproteinase 2 in the tumor microenvironment.Molecular and cellular therapies · 2014Review
- Cardiac matrix: a clue for future therapy.Biochimica et biophysica acta · 2013Review
- Antagonism of VEGF-A-induced increase in vascular permeability by an integrin α3β1-Shp-1-cAMP/PKA pathway.Blood · 2012Article
- Nanostructured, self-assembling peptide K5 blocks TNF-α and PGE₂ production by suppression of the AP-1/p38 pathway.Mediators of inflammation · 2012Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Tissue inhibitor of metalloproteinases-2 (TIMP-2) inhibits angiogenesis by several mechanisms involving either MMP inhibition or direct endothelial cell binding. The primary aim of this study was to identify the TIMP-2 region involved in binding to the previously identified receptor integrin α3β1, and to determine whether synthetic peptides derived from this region retained angio-inhibitory and tumor suppressor activity. We demonstrated that the N-terminal domain of TIMP-2 (N-TIMP-2) binds to α3β1 and inhibits vascular endothelial growth factor-stimulated endothelial cell growth in vitro, suggesting that both the α3β1-binding domain and the growth suppressor activity of TIMP-2 localize to the N-terminal domain. Using a peptide array approach we identify a 24 amino acid region of TIMP-2 primary sequence, consisting of residues Ile43-Ala66, which shows α3β1-binding activity. Subsequently we demonstrate that synthetic peptides from this region compete for TIMP-2 binding to α3β1 and suppress endothelial growth in vitro. We define a minimal peptide sequence (peptide 8-9) that possesses both angio-inhibitory and, using a murine xenograft model of Kaposi's sarcoma, anti-tumorigenic activity in vivo. Thus, both the α3β1-binding and the angio-inhibitory activities co-localize to a solvent exposed, flexible region in the TIMP-2 primary sequence that is unique in amino acid sequence compared with other members of the TIMP family. Furthermore, comparison of the TIMP-2 and TIMP-1 protein 3-D structures in this region also identified unique structural differences. Our findings demonstrate that the integrin binding, tumor growth suppressor and in vivo angio-inhibitory activities of TIMP-2 are intimately associated within a unique sequence/structural loop (B-C loop).
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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.