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

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, Jasti S. Rao

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3369-3373
Number of pages5
JournalCancer Research
Volume59
Issue number14
StatePublished - Jul 15 1999

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. (1999). Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth. Cancer Research, 59(14), 3369-3373.