Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2004-4-6
pubmed:abstractText
Urokinase-type plasminogen activator (uPA) degrades the extracellular matrix and plays critical roles in tumor invasion and metastasis. Matriptase, a membrane-bound serine protease, was shown to activate uPA in a uPA receptor-free, solution-based study. We now investigate whether matriptase affects activation of receptor-bound uPA and contributes to the invasiveness of HRA human ovarian cancer cells in vitro and tumor behavior in nude mice. Here we show the following. 1) uPA expression was effectively stimulated by TGF-beta1 in HRA cells. 2) Antisense (AS)-matriptase transfection achieved a marked inhibition of receptor-bound pro-uPA activation without altering expression of uPA and uPA receptor mRNA and proteins, irrespective of whether cells were stimulated with TGF-beta1. 3) Tumor cell receptor-bound pro-uPA could be efficiently cleaved by matriptase to generate enzymatically active two-chain uPA. Thus, matriptase can substitute for plasmin in the proteolytic activation of pro-uPA to enzymatically active uPA. 4) The AS-matriptase-treated cells had a decreased ability to invade an extracellular matrix layer, as compared with control cells. 5) When the AS-matriptase-treated cells were injected intraperitoneally into nude mice, the mice developed smaller tumors. Our data identify a novel role for matriptase for activation of receptor-bound uPA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Coloring Agents, http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/Fibrinolysin, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense, http://linkedlifedata.com/resource/pubmed/chemical/PLAUR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Plaur protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Urokinase Plasminogen..., http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/SPINT2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tetrazolium Salts, http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1, http://linkedlifedata.com/resource/pubmed/chemical/Trypsin Inhibitor, Kunitz Soybean, http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator, http://linkedlifedata.com/resource/pubmed/chemical/matriptase, http://linkedlifedata.com/resource/pubmed/chemical/saruplase, http://linkedlifedata.com/resource/pubmed/chemical/thiazolyl blue
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14899-908
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14747469-Animals, pubmed-meshheading:14747469-Binding, Competitive, pubmed-meshheading:14747469-Blotting, Northern, pubmed-meshheading:14747469-Blotting, Western, pubmed-meshheading:14747469-Cell Line, Tumor, pubmed-meshheading:14747469-Cell Membrane, pubmed-meshheading:14747469-Coloring Agents, pubmed-meshheading:14747469-Culture Media, Conditioned, pubmed-meshheading:14747469-DNA, Complementary, pubmed-meshheading:14747469-Dose-Response Relationship, Drug, pubmed-meshheading:14747469-Down-Regulation, pubmed-meshheading:14747469-Extracellular Matrix, pubmed-meshheading:14747469-Fibrinolysin, pubmed-meshheading:14747469-Flow Cytometry, pubmed-meshheading:14747469-Genome, pubmed-meshheading:14747469-Humans, pubmed-meshheading:14747469-Membrane Glycoproteins, pubmed-meshheading:14747469-Mice, pubmed-meshheading:14747469-Neoplasm Invasiveness, pubmed-meshheading:14747469-Neoplasm Transplantation, pubmed-meshheading:14747469-Oligonucleotides, Antisense, pubmed-meshheading:14747469-Peritoneal Neoplasms, pubmed-meshheading:14747469-Protein Binding, pubmed-meshheading:14747469-Receptors, Cell Surface, pubmed-meshheading:14747469-Receptors, Urokinase Plasminogen Activator, pubmed-meshheading:14747469-Recombinant Proteins, pubmed-meshheading:14747469-Serine Endopeptidases, pubmed-meshheading:14747469-Tetrazolium Salts, pubmed-meshheading:14747469-Thiazoles, pubmed-meshheading:14747469-Time Factors, pubmed-meshheading:14747469-Transfection, pubmed-meshheading:14747469-Transforming Growth Factor beta, pubmed-meshheading:14747469-Transforming Growth Factor beta1, pubmed-meshheading:14747469-Trypsin Inhibitor, Kunitz Soybean, pubmed-meshheading:14747469-Urokinase-Type Plasminogen Activator
pubmed:year
2004
pubmed:articleTitle
Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase.
pubmed:affiliation
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't