Osteopontin Ribozymes in Prostate Cancer Cells: Application to Bony Metastases
Abstract
Bone represents a common Site for metastasis of prostate cancer cells, where the invading cells find themselves in an environment rich in factors which promote cancer growth and progression. Genetic changes occur during disease progression in bone which include both gene mutation and changes in the pattern of gene expression. These genetic alterations provide targets for new "molecular drugs' for metastatic prostate cancer, This project will investigate the role of an extracellular matrix protein, osteopontin, which is expressed by metastatic prostate cancer cells but not by normal prostate in the ability of prostate cancer cells to form metastases in bone. The functional properties of osteopontin, including interactions with the alphavbeta3 integrin and CD44 receptor, indicate that osteopontin may play an important role in tumor cell attachment, invasion and growth in the bone environment. A series of ribozymes which specifically cleave OPN mRNA seguences will be developed that will inhibit expression of the osteopontin gene. A series of experiments will be performed in stable transfected prostate cancer cell lines to determine if ribozyme-mediated destruction of the osteopontin gene product modulates cell phenotype. In particular we will examine effects on adhesive properties, growth in soft agar, cell growth rates, chemotaxis, and invasion. These studies will be designed to translate into improved therapies aimed at inhibiting the development of prostate cancer at secondary bony sites. They will also allow development of a prototype-for molecular constructs that could be targeted for treatment of other types of cancer that can metastasize to the bones.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADA398209
Entities
People
- Cindy Farach-carson
Organizations
- University of Delaware