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Retroviral display of urokinase-binding domain fused to amphotropic envelope protein.

Abstract
Tumors frequently express urokinase (uPA) receptor (uPAR). To investigate whether uPAR can efficiently target cancerous cells using amphotropic retroviral vectors, we generated a retrovirus displaying the amino-terminal fragment (ATF) of uPA as an N-terminal extension of viral envelope protein. We also made use of a "two-step strategy" by inserting a uPA cleavage site between the ATF moiety and the envelope. We measured the ability of ATF-bearing chimeric envelopes to infect huPAR-overexpressing Madin-Darby canine kidney (MDCK) and control MDCK II cells. The ATF-viruses infected both MDCK cell lines with an equivalent efficiency, suggesting that the chimeric viruses were not sequestered by uPAR and infect cells preferentially via the Pit-2 receptor. The addition of a uPA cleavage site increased the infection level of huPAR-MDCK cells by 2-fold when uPA was present in the infection medium. Surprisingly, ATF-env viruses infected huPAR-MDCK cells 5.5-fold more efficiently in the presence of exogenous uPA. This stimulatory effect of uPA on infection of huPAR-MDCK cells by the ATF-env virus was completely abolished by methyl-beta-cyclodextrin, suggesting that this effect involves the caveolar endocytosis pathway.
AuthorsAntoine Boucquey, Frederik Vilhardt, Tatjana Mitrovic, Dominique Franco, Anne Weber, Philippe Horellou
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 331 Issue 4 Pg. 1485-93 (Jun 17 2005) ISSN: 0006-291X [Print] United States
PMID15883041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA Primers
  • Viral Envelope Proteins
  • Urokinase-Type Plasminogen Activator
Topics
  • Animals
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Dogs
  • Retroviridae (genetics)
  • Urokinase-Type Plasminogen Activator (metabolism)
  • Viral Envelope Proteins (metabolism)

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