ArticleHepatology (Baltimore, Md.)2015
Tissue inhibitor of metalloproteinases (TIMP)-1 creates a premetastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice.
Article in Hepatology (Baltimore, Md.), 2015. 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, 208 citations in OpenAlex.
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- Platelet-neutrophil cooperation in cancer: mechanisms of metastatic niche formation and implications for prognostic stratification and therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- Inhalable perfluorocarbon RNA nanocapsules overcome biological barriers to treat lung metastases.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Orchestrating the pre-metastatic niche: roles of stromal mediators and immune cells in metastatic progression and therapeutic targeting.Frontiers in immunology · 2026Review
- Organ-specific pre-metastatic and metastatic niches in colorectal cancer: "discrepancy in response to immune checkpoint inhibitors in liver and lung metastasis".Frontiers in immunology · 2026Review
- Review of the premetastatic niche in liver cancer bone metastases.International journal of clinical and experimental pathology · 2026Review
- The Pre-metastatic Niche-related Index Reveals the Immune Signature and Immunotherapy Response in Lung Adenocarcinoma.Current medicinal chemistry · 2026Article
- Integrin-Mediated TIMP1 Signaling Reprograms Liver Macrophages and Accelerates Colorectal Cancer Metastasis.Cells · 2025Article
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
- Liver metastasis of colorectal cancer: Mechanism and clinical therapy (Review).Oncology reports · 2025Review
- Neutrophils in cancer: At the crucial crossroads of anti-tumor and pro-tumor.Cancer communications (London, England) · 2025Review
- Metastatic heterogeneity in pancreatic cancer: mechanisms and opportunities for targeted intervention.The Journal of clinical investigation · 2025Review
- Understanding pre-metastatic niche formation: implications for colorectal cancer liver metastasis.Journal of translational medicine · 2025Review
- Review
- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Inflammation and Immunity in Liver Neoplasms: Implications for Future Therapeutic Strategies.Molecular cancer therapeutics · 2025Review
- Tissue inhibitor of metalloproteinase 1 as a biomarker of venous invasion in pancreatic ductal adenocarcinoma.American journal of cancer research · 2025Article
- Prognostic value of metal-based ferroptosis and cuproptosis genes and score in lower grade gliomas.Frontiers in immunology · 2025Article
- The Role of Myeloid Cells on the Development of Hepatic Metastases in Gastrointestinal Cancer.Gastro hep advances · 2025Review
81 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledDue to its ability to inhibit prometastatic matrix metalloproteinases, tissue inhibitor of metalloproteinases (TIMP)-1 has been thought to suppress tumor metastasis. However, elevated systemic levels of TIMP-1 correlate with poor prognosis in cancer patients, suggesting a metastasis-stimulating role of TIMP-1. In colorectal cancer patients, tumor as well as plasma TIMP-1 levels were correlated with synchronous liver metastasis or distant metastasis-associated disease relapse. In mice, high systemic TIMP-1 levels increased the liver susceptibility towards metastasis by triggering the formation of a premetastatic niche. This promoted hepatic metastasis independent of origin or intrinsic metastatic potential of tumor cells. High systemic TIMP-1 led to increased hepatic SDF-1 levels, which in turn promoted recruitment of neutrophils to the liver. Both inhibition of SDF-1-mediated neutrophil recruitment and systemic depletion of neutrophils reduced TIMP-1-induced increased liver susceptibility towards metastasis. This indicates a crucial functional role of neutrophils in the TIMP-1-induced premetastatic niche.
conclusionOur results identify TIMP-1 as an essential promoter of hepatic premetastatic niche formation.
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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.