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 was to test whether an antibody against PTHrP will block prostate cancer metastasis to bone. I cloned 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 a bicistronic expression vector produced mouse lgG when transfected into human 293 cells. Secreted mouse antibody inhibited osteoclast formation and bone resorption in two tissue culture assays stimulated with PTHrP. The DNA was transfected into the human prostate cancer cell line PC3, which secretes PTHrP and causes osteolytic metastases. No stable clones could be obtained. Instead, PC3 clones with decreased PTHrP consequent to a dominant negative TGFbeta receptor were tested for their ability to metastasize to bone in animals. Paradoxically, bone metastases were made worse by the dominant negative receptor. This may be due to effects on lGFBP3 expression by PC3 cells. In my fellowship I learned many molecular and immunological techniques in the first year. In the second year I learned animal techniques related to bone metastases, including quantitative x-ray image analysis and skeletal histomorphometry.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2002
- Accession Number
- ADA421761
Entities
People
- Xiuhua Sun
Organizations
- University of Texas Health Science Center at San Antonio