Document Detail


Reversion of the invasive phenotype of transformed human fibroblasts by anti-messenger oligonucleotide inhibition of urokinase receptor gene expression.
MedLine Citation:
PMID:  7805047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The receptors for urokinase plasminogen activator were studied in both normal human fibroblasts (WI-38 cells) and their SV40-transformed counterpart (VA-13 cells). We have shown that transformed cells expose 10 times more urokinase plasminogen activator receptors (u-PAR) than normal cells. By cross-linking aliquots of cell lysates with the aminoterminal fragment of the A chain of u-PA, containing the receptor-binding sequence, we have observed a u-PAR concentration at focal contacts in both cell lines. Only transformed cells were able to efficiently invade the basement membrane Matrigel. Switching off the receptor gene expression by the anti-messenger oligodeoxynucleotides strategy abolished the invasive properties of transformed cells. The anti-messenger oligodeoxynucleotide sequence we have designed inhibited the u-PAR gene expression, lowering both the receptor and the receptor mRNA. This indicates that overexpression of u-PAR gene is itself responsible for invasivity of transformed fibroblasts in our cell model system and that antisense compound therapy may prove to be of clinical interest in the control of cancer spreading.
Authors:
A Quattrone; G Fibbi; E Anichini; M Pucci; A Zamperini; S Capaccioli; M Del Rosso
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  55     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1995 Jan 
Date Detail:
Created Date:  1995-01-30     Completed Date:  1995-01-30     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  90-5     Citation Subset:  IM    
Affiliation:
Istituto di Patologia Generale, Università di Firenze, Italy.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cell Transformation, Viral
Cells, Cultured
Fibroblasts
Humans
Molecular Sequence Data
Neoplasm Invasiveness*
Oligonucleotides, Antisense / pharmacology*
Plasminogen Activators / metabolism
Receptors, Cell Surface / metabolism*
Receptors, Urokinase Plasminogen Activator
Simian virus 40
Urokinase-Type Plasminogen Activator / metabolism
Chemical
Reg. No./Substance:
0/Oligonucleotides, Antisense; 0/PLAUR protein, human; 0/Receptors, Cell Surface; 0/Receptors, Urokinase Plasminogen Activator; EC 3.4.21.-/Plasminogen Activators; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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