Cellular Mechanisms Regulating Urokinase-Type Plasminogen Activator in Hormone Refractory Prostate Cancer: A Novel Therapeutic Target
Abstract
"Cellular Mechanisms Regulating Urokinase-Type Plasminogen Activator in Hormone Refractory Prostate Cancer: A Novel Therapeutic Target" has as its primary goals inhibiting the expression of two pathways critical to prostate cancer progression, one mediated by the tyrosine kinase receptor c-Met, and the second mediated by urokinase plasminogen activator (uPA), and determining the effects on tumor progression and metastasis. The purpose of the research is to provide a novel therapeutic basis for the development of prostate tumor metastases through inhibition of these growth regulatory pathways. Inhibition of the c-Met pathway through the use of an adenovirus expressing a specific ribozyme inhibits migration and invasion of prostate tumor cells in vitro and completely inhibits the growth and lymph node metastasis of prostate tumor cells in an orthotopic mouse model system (Kim et al., in Press). Direct inhibition of uPAR (urokinase plasminogen activator receptor), achieved by the competitive inhibitor for uPA binding, A6, also reduced invasive potential of prostate tumor cells in vitro, and greatly prolonged the survival of mice bearing prostate tumors (%survival" being defined as time to first signs of morbidity) Boyd et al., 2003). Thus, in the past year, we have nearly finished the first two tasks of the Award, with data demonstrating the c-Met and uPAR are both involved in tumor progression through cell migration and invasion and that both c-Met and uPAR are targets for therapeutic intervention. We plan to determine the effects of combining inhibitors of these two molecules and examine human tumors (task 3) in the final year of the work.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA417778
Entities
People
- Gary E. Gallick
Organizations
- The University of Texas MD Anderson Cancer Center