| http://purl.uniprot.org/citations/18681831 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18681831 | http://www.w3.org/2000/01/rdf-schema#comment | "Formation of multiple and scattered metastases in target organs, leading to disruption of organ functional integrity, is the death-determining step for most lethal cancers. In the clinic, elevated expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) is often associated with increased aggressiveness of cancer. We demonstrated that elevated host expression of TIMP-1 leads to the promotion of scattered liver metastases in mice, associated with increased activity of cysteine proteases (CPs). This study aimed for reduction of TIMP-1-promoted experimental liver metastases of lacZ-tagged human fibrosarcoma cells by overexpression of cystatin C, a natural inhibitor of CPs, in the murine host. Although CP inhibition reduced TIMP-induced proteolytic activity, the TIMP-1-induced increase in total tumor cell burden in livers was not significantly reduced. However, overexpression of cystatin C in livers with elevated TIMP-1 led to the formation of large multicellular metastatic foci in 42% of the mice. This formation was associated with increased expression of plasminogen activators (PAs). Additional overexpression of plasminogen activator inhibitor-2 prevented the formation of macrometastatic foci as well as the TIMP-1-induced increase in total tumor cell burden. This demonstrates that PAs are crucial for the prometastatic activity of TIMP-1 and led to the assumption that patients with elevated TIMP-1 expression may benefit from an antiproteolytic treatment directed against PAs."xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.org/dc/terms/identifier | "doi:10.1089/hum.2008.078"xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/author | "Kruger A."xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/author | "Gansbacher B."xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/author | "Gerg M."xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/author | "Kopitz C."xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/name | "Hum Gene Ther"xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/pages | "1039-1049"xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/title | "Plasminogen activator inhibitor-2, but not cystatin C, inhibits the prometastatic activity of tissue inhibitor of metalloproteinases-1 in the liver."xsd:string |
| http://purl.uniprot.org/citations/18681831 | http://purl.uniprot.org/core/volume | "19"xsd:string |
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