Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines
Φόρτωση...
Ημερομηνία
Συγγραφείς
Lakka, S. S.
Rajagopal, R.
Rajan, M. K.
Mohan, P. M.
Adachi, Y.
Dinh, D. H.
Olivero, W. C.
Gujrati, M.
Ali-Osman, F.
Roth, J. A.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Clin Cancer Res
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in the proteolytic cascade involved in the metastasis of lung and other cancers. We report that the reduction in uPAR levels produced by an antisense strategy using an adenovirus construct (Ad-uPAR) in H1299 cells, an invasive human lung cancer cell line that produces high levels of uPAR, resulted in a decrease of uPAR levels to 80-90% of those seen in cells infected with mock or adenovirus (Ad)-cytomegalovirus vector controls. In addition, increasing the multiplicity of infection from 25 to 200 caused a corresponding decrease in the level of uPAR protein within 5 days of treatment, as shown by Western blot analysis. Furthermore, the in vitro translation of total RNA levels of Ad-uPAR-infected H1299 cells in a rabbit reticulocyte lysate system caused a 50-70% decrease in uPAR immunoprecipitate in Ad-uPAR-infected cells relative to the levels in cells of mock and vector controls. The Matrigel invasion assay showed the invasion of H1299 cells and A549 cells infected with Ad-uPAR to be decreased by 70% relative to mock- and vector-infected controls. Infection of tumor cells with Ad-uPAR before implantation significantly reduced the incidence of lung metastasis by 85% as compared with the control virus-infected cells injected into nude mice through the tail vein. Our collective results show that the uPAR system is a potential target of treatment for lung cancers.
Περιγραφή
Λέξεις-κλειδιά
Adenoviridae/genetics, Animals, Carcinoma, Non-Small-Cell Lung/*drug therapy/secondary, DNA, Antisense/genetics/pharmacology/*therapeutic use, Female, Gene Transfer Techniques, Genetic Vectors, Lung Neoplasms/*drug therapy/pathology, Mice, Neoplasm Invasiveness, Neoplasm Transplantation, Protein Biosynthesis/drug effects, RNA, Messenger/drug effects/metabolism, Receptors, Cell Surface/*antagonists & inhibitors/genetics/metabolism, Receptors, Urokinase Plasminogen Activator, Tumor Cells, Cultured, Xenograft Model Antitumor Assays
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/11309361
http://clincancerres.aacrjournals.org/content/7/4/1087.full.pdf
http://clincancerres.aacrjournals.org/content/7/4/1087.full.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής