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- W1633784490 abstract "Due 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.Our results identify TIMP-1 as an essential promoter of hepatic premetastatic niche formation." @default.
- W1633784490 created "2016-06-24" @default.
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- W1633784490 date "2014-11-24" @default.
- W1633784490 modified "2023-10-18" @default.
- W1633784490 title "Tissue inhibitor of metalloproteinases (TIMP)‐1 creates a premetastatic niche in the liver through SDF‐1/CXCR4‐dependent neutrophil recruitment in mice" @default.
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- W1633784490 doi "https://doi.org/10.1002/hep.27378" @default.
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