Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth (Journal article)

Mohan, P. M./ Chintala, S. K./ Mohanam, S./ Gladson, C. L./ Kim, E. S./ Gokaslan, Z. L./ Lakka, S. S./ Roth, J. A./ Fang, B./ Sawaya, R./ Kyritsis, A. P./ Rao, J. S.

The urokinase-type plasminogen activator (uPA) and uPA receptor (UPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. sc. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR-infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established so U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adenoviridae/*genetics,Animals,Brain Neoplasms/pathology/*therapy,DNA, Antisense/*genetics,Disease Progression,*Gene Therapy,Glioblastoma/pathology/*therapy,Humans,Mice,Mice, Nude,Neoplasm Invasiveness,Neoplasm Proteins/antagonists & inhibitors/*genetics,Neoplasm Transplantation,Organoids,Rats,Receptors, Cell Surface/antagonists & inhibitors/*genetics,Receptors, Urokinase Plasminogen Activator,Tumor Cells, Cultured
ISSN: 0008-5472
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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