ArticleJournal of cellular and molecular medicine2010
Tissue inhibitor of metalloproteinases-1-induced scattered liver metastasis is mediated by host-derived urokinase-type plasminogen activator.
Article in Journal of cellular and molecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
- Colorectal liver metastasis: molecular mechanism and interventional therapy.Signal transduction and targeted therapy · 2022Review
- The hepatic pre-metastatic niche in pancreatic ductal adenocarcinoma.Molecular cancer · 2018Review
- PARP-1 promotes tumor recurrence after warm ischemic liver graft transplantation via neutrophil recruitment and polarization.Oncotarget · 2017Article
- Premetastatic niche formation in the liver: emerging mechanisms and mouse models.Journal of molecular medicine (Berlin, Germany) · 2015Review
- Molecular targets and pathways involved in liver metastasis of colorectal cancer.Clinical & experimental metastasis · 2015Review
- Impact of proteolytic enzymes in colorectal cancer development and progression.World journal of gastroenterology · 2014Review
- Metastasis review: from bench to bedside.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Review
- The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer.International journal of molecular sciences · 2012Review
- Tumor cell-derived Timp-1 is necessary for maintaining metastasis-promoting Met-signaling via inhibition of Adam-10.Clinical & experimental metastasis · 2011Article
- Matrix metalloproteinases in tumorigenesis: an evolving paradigm.Cellular and molecular life sciences : CMLS · 2011Review
- Tissue inhibitor of metalloproteinases-1-induced scattered liver metastasis is mediated by hypoxia-inducible factor-1α.Clinical & experimental metastasis · 2011Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paradoxically, not only proteinases but also their inhibitors can correlate with bad prognosis of cancer patients, underlining the evolving concept of the protease web as the complex interplay between proteinases, their inhibitors and effector molecules. Elevated levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) render the liver more susceptible to metastasis by triggering urokinase plasminogen activator (uPA) expression as well as hepatocyte growth factor (HGF) signalling, thereby leading to the fatal scattered infiltration of metastasizing tumour cells throughout the parenchyma of the target organ. Here, we investigated whether host uPA is a crucial protagonist for the TIMP-1-induced modulation of a pro-metastatic microenvironment in the liver. Indeed, in livers of uPA-ablated mice elevated TIMP-1 levels did not trigger HGF signalling and did not promote metastasis of a murine T-lymphoma cell line. In contrast, lack of tumour cell-derived uPA induced by gene silencing did not interfere with this pro-metastatic pathway. Furthermore, host uPA was necessary for the recruitment of neutrophilic granulocytes and the associated increase of HGF in livers with elevated TIMP-1 levels. This newly identified co-operation between TIMP-1 and host uPA suggests that therapies, simultaneously interfering with pro- and anti-proteolytic pathways may be beneficial for patients with metastatic disease.
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