Development of a Biologic Basis for PSMA Targeting in Prostate Cancer
Abstract
PSMA is a strongly expressed protein in prostate cancer. It is a type two-membrane protein with a short 19 amino acid terminal piece inside the cell, a membrane-spanning region from amino acids 20 to 43, and the rest of the 750 amino acids residing outside of the cell. We discovered that PSMA has unique hydrolytic activity as a carboxypeptidase in releasing glutamate either from polygammaglutamated folate as a folate hydrolase or from N-acetylaspartylglutamate, NAAG, as a neuropeptidase. We observed that cells expressing PSMA were killed by polygammglutamated methotrexate while cells not expressing PSMA survived. This lead us to hypothesize those glutamated prodrugs that were substrates for PSMA may serve as therapeutic agents in the treatment of prostate cancer. Understanding the biology of PSMA function served as the basis of our application for funding.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2003
- Accession Number
- ADA417073
Entities
People
- Warren D. Heston