Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-8-7
pubmed:abstractText
The diffuse and extensive infiltration of malignant gliomas into the surrounding normal brain is believed to rely on modifications of the proteolysis of extracellular matrix components. A key molecule in regulating plasminogen-mediated extracellular proteolysis is the urokinase-type plasminogen activator (uPA). To investigate the role of uPA in the invasive process of brain tumors, we stably transfected a human glioblastoma cell line SNB19 with a vector capable of expressing an antisense transcript complementary to the 1020 bases at the 3' end of the uPA cDNA. Parental, vector-, and antisense construct-stably transfected cell lines were analyzed for uPA mRNA transcript by Northern blot analysis, for uPA enzyme activity by zymography, and for uPA protein levels by Western blotting. The levels of uPA mRNA, protein, and enzyme activities were significantly lower in antisense clones than in parental and vector controls. Radioreceptor binding studies demonstrated that uPA receptor levels remained the same in parental, vector-, and antisense-transfected cells. The antisense-transfected cells showed a markedly lower level of invasion in the Matrigel invasion assays, and their spheroids failed to invade the fetal rat brain aggregates in the coculture system. Green fluorescent protein (GFP) expressing parental and antisense transfectants was generated for detection in mouse brain tissue without any posttreatment. Intracerebral injection of antisense stable transfectants significantly reduced tumor formation compared with that in controls. Our results suggested that down-regulation of uPA expression may be a feasible approach to reducing the malignancy and invasiveness of glial tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2519-26
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11489835-Animals, pubmed-meshheading:11489835-Blotting, Northern, pubmed-meshheading:11489835-Blotting, Western, pubmed-meshheading:11489835-Brain, pubmed-meshheading:11489835-DNA, Antisense, pubmed-meshheading:11489835-Fibrin, pubmed-meshheading:11489835-Gene Therapy, pubmed-meshheading:11489835-Glioblastoma, pubmed-meshheading:11489835-Humans, pubmed-meshheading:11489835-Mice, pubmed-meshheading:11489835-Mice, Nude, pubmed-meshheading:11489835-Microscopy, Confocal, pubmed-meshheading:11489835-Neoplasm Invasiveness, pubmed-meshheading:11489835-Protein Binding, pubmed-meshheading:11489835-RNA, Messenger, pubmed-meshheading:11489835-Rats, pubmed-meshheading:11489835-Rats, Sprague-Dawley, pubmed-meshheading:11489835-Transfection, pubmed-meshheading:11489835-Tumor Cells, Cultured, pubmed-meshheading:11489835-Urokinase-Type Plasminogen Activator, pubmed-meshheading:11489835-Xenograft Model Antitumor Assays
pubmed:year
2001
pubmed:articleTitle
Stable transfection of urokinase-type plasminogen activator antisense construct modulates invasion of human glioblastoma cells.
pubmed:affiliation
Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61656, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.