Targeted Antibody Inhibition of Bone Metastases by Prostate Cancer
Abstract
Metastasis to bone is a major cause of morbidity from prostate cancer. Parathyroid hormone related protein (PTHrP) is expressed by prostate cancer cells and stimulates osteoclasts. My project to test whether an antibody against PTHrP will block prostate cancer metastasis to bone. I clone the light and heavy chain cDNAs from a hybridoma, which secretes a PTHrP-neutralizing antibody which blocks breast cancer metastasis to bone but is untested against prostate cancer. The cDNAs in bicistronic expression vector produced mouse lgG when transfected into human 293 cells. Secrete mouse antibody inhibited osteoclast formation and bone resorption in two tissue culture assay stimulated with 2onglmL PTHrP (1-34) peptide. Next, the DNA will be transfected into the human prostate cancer cell line PC3, which secretes PTHrP and causes osteolytic metastases. PC3 clone which neutralize their own PTHrP will be tested for their ability to metastasize to bone in animals, which is expected to be greatly reduced compared to controls. In the first year of my fellowship I have learned many molecular and immunological techniques. In the second year I will learn many animal technique related to bone metastases, including quantitative x-ray image analysis and skeletal histomorphometry.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA385860
Entities
People
- John Chirgwin
- Xiuhua Sun
Organizations
- University of Texas at San Antonio