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.
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Authors | Antoine Boucquey, Frederik Vilhardt, Tatjana Mitrovic, Dominique Franco, Anne Weber, Philippe Horellou |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 331
Issue 4
Pg. 1485-93
(Jun 17 2005)
ISSN: 0006-291X [Print] United States |
PMID | 15883041
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- Viral Envelope Proteins
- Urokinase-Type Plasminogen Activator
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Topics |
- Animals
- Base Sequence
- Cell Line
- DNA Primers
- Dogs
- Retroviridae
(genetics)
- Urokinase-Type Plasminogen Activator
(metabolism)
- Viral Envelope Proteins
(metabolism)
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