Both osteosarcoma and androgen-independent prostate cancers remain major challenges for the orthopedists, urologists and medical oncologists involved in the care of these patients. These seemingly unrelated diseases, however, came together through a molecular analysis of the gene(s) that may be over-expressed in these two forms of cancer during disease progression. Osteocalcin, a noncollagenous Gla protein, was thought to be produced specically in osteoblasts. OC is synthesized, secreted and deposited at the time of bone mineralization (Price, 1985). Interestingly, OC expression was upregulated in several forms of solid tumors, including osteosarcoma and both androgen-dependent and androgen-independent human prostate cancer cell lines. Furthermore, OC expression and secretion were higher in men with metastatic prostate cancer (Coleman et al., 1988; Curatolo et al., 1992), and serum levels of OC were even higher in prostate cancer patients subjected to hormonal deprivation, suggesting that OC may be negatively regulated by testicular androgen (Tarle et al., 1989).
B. Osteocalcin promoter-based tissue-specic gene therapy (Ad-OC-TK) for osteosarcoma 1. Molecular rationale Osteocalcin is a molecular marker present in the serum of patients suffering from either osteosarcoma or prostate cancer. A recent study showed that immunohistochemical staining of osteocalcin was positive in primary osteoblastic osteosarcoma and chondroblastic osteosarcoma specimens, as well as in ve of seven broblastic osteosarcomas. We have shown that strong osteocalcin staining was associated with both primary and metastatic prostate cancer (Ou et al., 1998). Since osteocalcin is the protein most commonly secreted by osteosarcoma cells of the osteoblastic lineage and also a marker of osteoblastic differentiation, we have chosen to use the osteocalcin promoter to achieve tissue-specic expression of the toxic TK gene in rat and human osteogenic sarcoma