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[Cancer Research 59, 3369-3373, July 1, 1999]
© 1999 American Association for Cancer Research

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[Cancer Research 59, 3369-3373, July 15, 1999]
© 1999 American Association for Cancer Research


Advances in Brief

Adenovirus-mediated Delivery of Antisense Gene to Urokinase-type Plasminogen Activator Receptor Suppresses Glioma Invasion and Tumor Growth1

Pamarthi M. Mohan, Shravan K. Chintala, Sanjeeva Mohanam, Candece L. Gladson, Eui So Kim, Ziya L. Gokaslan, Sajani S. Lakka, Jack A. Roth, Bingliang Fang, Raymond Sawaya, Athanassios P. Kyritsis and Jasti S. Rao2

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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Copyright © 1999 by the American Association for Cancer Research.