Linked Life Data

12956426

Source:http://linkedlifedata.com/resource/pubmed/id/12956426

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2003-9-5
pubmed:abstractText
Several proteolytic systems are involved in (anti)adhesive, migratory, and proteolytic processes, necessary for tumor progression and metastasis. We analyzed whether multifunctional inhibitors of different tumor-associated proteolytic systems reduce tumor growth and spread of human ovarian cancer cells in vivo. Bifunctional inhibitors are composed of the N-terminal domain of either the human matrix metalloproteinase inhibitors TIMP-1 or TIMP-3 and the cysteine protease inhibitor chicken cystatin (chCysWT); trifunctional inhibitors are composed of N-TIMP-1 or -3 and a chicken cystatin variant harboring the uPAR binding site of uPA, chCys-uPA19-31, which in addition to its inhibitory activity toward cysteine proteases interferes with the interaction of the serine protease uPA with its receptor. OV-MZ-6#8 cancer cells, stably transfected with plasmids expressing the multifunctional inhibitors, displayed similar proliferative and adhesive features as the vector-transfected control, but showed significant reduction in their invasive behavior in vitro. The cell lines expressing the multifunctional inhibitors were inoculated into the peritoneum of nude mice. Expression of three of the four inhibitor variants (N-hTIMP-1-chCysWT, N-hTIMP-1-chCys-uPA19-31, and N-hTIMP-3-chCysWT) resulted in a significant reduction of tumor burden compared to the vector-control cell line. These compact and small inhibitors may represent promising agents for gene therapy of solid malignant tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1431-6730
pubmed:author
pubmed:issnType
Print
pubmed:volume
384
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1097-102
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12956426-Animals, pubmed-meshheading:12956426-Cell Line, Tumor, pubmed-meshheading:12956426-Cysteine Proteinase Inhibitors, pubmed-meshheading:12956426-Endopeptidases, pubmed-meshheading:12956426-Female, pubmed-meshheading:12956426-Mice, pubmed-meshheading:12956426-Mice, Nude, pubmed-meshheading:12956426-Neoplasm Invasiveness, pubmed-meshheading:12956426-Neoplasm Transplantation, pubmed-meshheading:12956426-Ovarian Neoplasms, pubmed-meshheading:12956426-Peritoneal Neoplasms, pubmed-meshheading:12956426-Plasmids, pubmed-meshheading:12956426-Receptors, Cell Surface, pubmed-meshheading:12956426-Receptors, Urokinase Plasminogen Activator, pubmed-meshheading:12956426-Recombinant Proteins, pubmed-meshheading:12956426-Tissue Inhibitor of Metalloproteinase-1, pubmed-meshheading:12956426-Tissue Inhibitor of Metalloproteinase-3, pubmed-meshheading:12956426-Transfection
pubmed:year
2003
pubmed:articleTitle
Inhibition of intraperitoneal tumor growth of human ovarian cancer cells by bi- and trifunctional inhibitors of tumor-associated proteolytic systems.
pubmed:affiliation
Klinische Forschergruppe der Frauenklinik, Technische Universität München, Klinikum rechts der Isar, D-81675 München, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't