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Tissue inhibitor of metalloproteinases (TIMP)-1 creates a premetastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2015 Jan; Vol. 61 (1), pp. 238-48. Date of Electronic Publication: 2014 Nov 24. - Publication Year :
- 2015
-
Abstract
- Unlabelled: 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.<br />Conclusion: Our results identify TIMP-1 as an essential promoter of hepatic premetastatic niche formation.<br /> (© 2014 by the American Association for the Study of Liver Diseases.)
- Subjects :
- Animals
Carcinoma blood
Cell Line, Tumor
Humans
Liver immunology
Liver metabolism
Liver Neoplasms blood
Mice
Mice, Inbred Strains
NIH 3T3 Cells
Tissue Inhibitor of Metalloproteinase-1 blood
Carcinoma secondary
Chemokine CXCL12 metabolism
Liver Neoplasms secondary
Neutrophil Infiltration
Receptors, CXCR4 metabolism
Tissue Inhibitor of Metalloproteinase-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 61
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 25131778
- Full Text :
- https://doi.org/10.1002/hep.27378