Studies of Role of Cathepsin K and Inhibitory Effects of Bisphosphonates in Prostate Cancer Bone Metastasis

摘要

Prostate cancer (Cap) is often associated with bone metastases, which cause much of the morbidity associated with Cap. CaP bone metastases exhibit increases in both bone formation and resorption. Zn studies under this award, we have investigated the expression and activity of Cathepsin K (Cat K), an enzyme involved in bone lysis in CaP in vitro and in vivo. The Cat K message and protein were detected in CaP cell lines, primary Cap samples, and metastatic samples. Expression of Cat K in bone metastases was significantly higher than in primary CaP. Cat K enzymatic activity was detected in CaP cell lines. ZA decreased the proliferation of CaP cells and caused apoptosis of CaP cells in vitro. Zn vivo, growth of osteoblastic and osteolytic metastases of CaP was significantly inhibited; however, growth of subcutaneous tumors was unaffected by ZA, indicating that he growth inhibition effects were directly related to the interactions between ZA and bone, and/or CaP metastases in bone. Treatment of C4-2 mixed CaP bone metastases resulted in decreased numbers of osteoclasts, but the effects on tumor volume were method-dependent. Evaluation of the effects of ZA on bone seeding, using cardiac injection model, is ongoing.