Cellular Mechanisms Regulating uPA in Hormone Refractory Prostate Cancer: A Novel Therapeutic Target
Abstract
DOD Award number DAMD17-00-1-0524, "Cellular Mechanisms Regulating Urokinase-Type Plasminogen Activator in Hormone Refractory Prostate Cancer: A Novel Therapeutic Target" has its goal 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). 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. In the past year, we have demonstrated in orthotopic mouse model systems that inhibition of both pathways greatly decreases tumorigenicity and metastatic potential of human prostate tumor cells. By inhibiting c-Met expression with an Adenovims expressing a c-Met ribozyme, tumorigenicity of PC3-LN4 cells (with high metastatic potential) was greatly reduced, and no metastases were formed. Inhibition of uPAR (urokinase plasminogen activator receptor), by the competitive inhibitor for uPA binding, A6, reduced tumorigenicity and metastatic potential. A6 also reduced cellular invasion. Thus, in the past year, we have made substantial progress in demonstrating the effectiveness of inhibition of two critical pathways in metastasis in mouse models, and providing new insights into the role of these molecules in the metastatic phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407621
Entities
People
- Gary E. Gallick
Organizations
- The University of Texas MD Anderson Cancer Center