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Departments of Neurosurgery [P. M. M., S. K. C., S. M., E. S. K., Z. L. G., S. S. L., R. S., J. S. R.], Thoracic and Cardiovascular Surgery [J. A. R., B. F.], and Neuro-Oncology [A. P. K.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of Pathology, University of Alabama, Birmingham, Alabama 35294 [C. L. G.]
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. s.c. (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 s.c. 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.
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