ArticleCarcinogenesis2020
TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer.
Article in Carcinogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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.
The trial behind it
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
50 citing papers in PubMed, 69 citations in OpenAlex.
- Bioinformatic Analysis of Contrasting Expression Patterns and Molecular Interactions of TIMPs in Breast Cancer: Implications for Tumor Progression and Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Mechanisms of Antiproliferative Effects of Nobiletin, Scoparone, and Tangeretin Isolated fromInternational journal of molecular sciences · 2026Article
- Extracellular vesicles delivering TIMP-2 modulate MMP-1, MMP-2, and MMP-9 expression in human lung adenocarcinoma A549 cells.Frontiers in pharmacology · 2026Article
- Evaluation of the Activity of Monensin and Its Analogs for Modulation of Stem-like Cell Functionality in 2D and 3D Breast Cancer Models.ACS pharmacology & translational science · 2025Article
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Deciphering the roles of non-coding RNAs in liposarcoma development: Challenges and opportunities for translational therapeutic advances.Non-coding RNA research · 2025Review
- Histidine Tag-Specific PEGylation Improves the Circulating Half-Life of TIMP2.ACS applied bio materials · 2025Article
- TIMP-2 Modulates 5-Fu Resistance in Colorectal Cancer Through Regulating JAK-STAT Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Arid4a Suppresses Breast Tumor Metastasis by Enhancing MTSS1 Expression via mRNA Stability.Cancer medicine · 2025Article
- A Review of Talin- and Integrin-Dependent Molecular Mechanisms in Cancer Invasion and Metastasis.International journal of molecular sciences · 2025Review
- Targeting the Molecules in EMT: A Potential Therapeutic Opportunity in Breast Cancer.Current molecular medicine · 2025Review
- Breast Cancer-Derived Extracellular Vesicles Modulate the Cytoplasmic and Cytoskeletal Dynamics of Blood-Brain Barrier Endothelial Cells.Journal of extracellular vesicles · 2025Article
- Nano-Drug Delivery Systems Targeting MMPs: A Promising Treatment for Gliomas.International journal of nanomedicine · 2025Review
- Machine learning and gene network integration reveal prognostic subnetworks and biomarkers in pancreatic cancer.Computational and structural biotechnology journal · 2025Article
- Engineered TIMP2 with narrow MMP-9 specificity is an effective inhibitor of invasion and proliferation of triple-negative breast cancer cells.The Journal of biological chemistry · 2024Article
- Mapping Extracellular Protein-Protein Interactions Using Extracellular Proximity Labeling (ePL).Journal of proteome research · 2024Article
- Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.Biomolecules · 2024Article
- DeepKINET: a deep generative model for estimating single-cell RNA splicing and degradation rates.Genome biology · 2024Article
- 3,4 Dihydroxyphenylethanol May Inhibit Metastasis in HepG2 Cells by Influencing the Expression of miR-21 and Genes Associated with Metastasis.Reports of biochemistry & molecular biology · 2024Article
- Improving Circulation Half-Life of Therapeutic Candidate N-TIMP2 by Unfolded Peptide Extension.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Metastasis is the primary cause of treatment failures and mortality in most cancers. Triple-negative breast cancer (TNBC) is refractory to treatment and rapidly progresses to disseminated disease. We utilized an orthotopic mouse model that molecularly and phenotypically resembles human TNBC to study the effects of exogenous, daily tissue inhibitor of metalloproteinase-2 (TIMP-2) treatment on tumor growth and metastasis. Our results demonstrated that TIMP-2 treatment maximally suppressed primary tumor growth by ~36-50% and pulmonary metastasis by >92%. Immunostaining assays confirmed disruption of the epithelial to mesenchymal transition (EMT) and promotion of vascular integrity in primary tumor tissues. Immunostaining and RNA sequencing analysis of lung tissue lysates from tumor-bearing mice identified significant changes associated with metastatic colony formation. Specifically, TIMP-2 treatment disrupts periostin localization and critical cell-signaling pathways, including canonical Wnt signaling involved in EMT, as well as PI3K signaling, which modulates proliferative and metastatic behavior through p27 phosphorylation/localization. In conclusion, our study provides evidence in support of a role for TIMP-2 in suppression of triple-negative breast cancer growth and metastasis through modulation of the epithelial to mesenchymal transition, vascular normalization, and signaling pathways associated with metastatic outgrowth. Our findings suggest that TIMP-2, a constituent of the extracellular matrix in normal tissues, may have both direct and systemic antitumor and metastasis suppressor effects, suggesting potential utility in the clinical management of breast cancer progression.
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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.