Document Detail


Expression of human recombinant plasminogen activators enhances invasion and experimental metastasis of H-ras-transformed NIH 3T3 cells.
MedLine Citation:
PMID:  2747645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The gene transfer technique was used to examine the role of plasminogen activator (PA) in the invasive and metastatic behavior of tumorigenic cells. H-ras-transformed NIH 3T3 clonal cells producing a very low level of PA were generated and further transfected with an expression plasmid containing a cDNA sequence encoding either the urokinase-type or the tissue-type human PA. Compared with the parental transformed cells, clonal cells expressing high levels of both types of recombinant PA invaded more rapidly through a basement membrane reconstituted in vitro. Furthermore, cells expressing high levels of recombinant urokinase-type PA also caused a higher incidence of pulmonary metastatic lesions after intravenous injection into nude mice. Both activities were reduced by the serine proteinase inhibitor EACA; invasion was also suppressed by antibodies blocking the activity of human PAs and by the synthetic collagenase inhibitor SC-44463. These findings provide direct genetic evidence for a causal role of PA in invasive and metastatic activities.
Authors:
J H Axelrod; R Reich; R Miskin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  9     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1989 May 
Date Detail:
Created Date:  1989-08-18     Completed Date:  1989-08-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2133-41     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Weizmann Institute of Science, Rehovot, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Basement Membrane / physiology
Cell Transformation, Neoplastic*
Gene Expression Regulation
Humans
Mice
Neoplasm Invasiveness
Neoplasm Metastasis
Plasminogen Activators / biosynthesis,  genetics*
Proto-Oncogenes
Chemical
Reg. No./Substance:
EC 3.4.21.-/Plasminogen Activators
Comments/Corrections

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