ArticleClinical & experimental metastasis2011
Tumor cell-derived Timp-1 is necessary for maintaining metastasis-promoting Met-signaling via inhibition of Adam-10.
Article in Clinical & experimental metastasis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- TIMP1 Derived from Mesenchymal Stem Cells Promotes Bladder Cancer Progression by Regulating the Formation of VDIMs through the RAP1 Pathway.International journal of biological sciences · 2026Article
- Bioinformatics mining and experimental validation of prognostic biomarkers in colorectal cancer.Discover oncology · 2025Article
- TIMP-1-expressing breast tumor spheroids for the evaluation of drug penetration and efficacy.Bioengineering & translational medicine · 2022Article
- Article
- The hepatic pre-metastatic niche in pancreatic ductal adenocarcinoma.Molecular cancer · 2018Review
- Distant Insulin Signaling Regulates Vertebrate Pigmentation through the Sheddase Bace2.Developmental cell · 2018Article
- Organ-specific metastases obtained by culturing colorectal cancer cells on tissue-specific decellularized scaffolds.Nature biomedical engineering · 2018Article
- Characterization of the catalytic properties of the membrane-anchored metalloproteinase ADAM9 in cell-based assays.The Biochemical journal · 2017Article
- Molecular Pathways: Receptor Ectodomain Shedding in Treatment, Resistance, and Monitoring of Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Review
- Article
- TIMPs: versatile extracellular regulators in cancer.Nature reviews. Cancer · 2017Review
- Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance.Cancer discovery · 2016Article
- Premetastatic niche formation in the liver: emerging mechanisms and mouse models.Journal of molecular medicine (Berlin, Germany) · 2015Review
- Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain.Scientific reports · 2015Article
- TIMP-1 signaling via CD63 triggers granulopoiesis and neutrophilia in mice.Haematologica · 2015Article
- Molecular targets and pathways involved in liver metastasis of colorectal cancer.Clinical & experimental metastasis · 2015Review
- Hepatic stellate cells: central modulators of hepatic carcinogenesis.BMC gastroenterology · 2015Review
- Down-regulation of TIMP-1 inhibits cell migration, invasion, and metastatic colonization in lung adenocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Tumor-Induced Local and Systemic Impact on Blood Vessel Function.Mediators of inflammation · 2015Review
- Tissue inhibitor of metalloproteinases (TIMP)-1 creates a premetastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice.Hepatology (Baltimore, Md.) · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In many different tumor entities, increased expression of tissue inhibitor of metalloproteinases-1 (Timp-1) is associated with poor prognosis. We previously reported in mouse models that elevated systemic levels of Timp-1 induce a gene expression signature in the liver microenvironment increasing the susceptibility of this organ to tumor cells. This host effect was dependent on increased activity of the hepatocyte growth factor (Hgf)/hepatocyte growth factor receptor (Met) signaling pathway. In a recent study we showed that Met signaling is regulated by Timp-1 as it inhibits the Met sheddase A disintegrin and metalloproteinase-10 (Adam-10). The aim of the present study was to elucidate whether the metastatic potential of tumor cells benefits from autocrine Timp-1 as well and involves Adam-10 and Met signaling. In a syngeneic murine model of experimental liver metastasis Timp-1 expression and Met signaling were localized within metastatic colonies and expressed by tumor cells. Knock down of tumor cell Timp-1 suppressed Met signaling in metastases and inhibited metastasis formation and tumor cell-scattering in the liver. In vitro, knock down of tumor cell Timp-1 prevented Hgf-induced Met phosphorylation. Consequently, knock down of Met sheddase Adam-10 triggered auto-phosphorylation and responsiveness to Hgf. Accordingly, Adam-10 knock down increased Met phosphorylation in metastatic foci and induced tumor cell scattering into the surrounding liver parenchyma. In conclusion, these findings show that tumor cell-derived Timp-1 acts as a positive regulator of the metastatic potential and support the concept that proteases and their natural inhibitors, as members of the protease web, are major players of signaling during normal homeostasis and disease.
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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.