Bone metastasis affects greater than 80 percent of patients with advanced prostate cancer, and this observed osteotropism has recently been correlated to bone SPARC content. We have previously defined a molecular pathway that illuminates the role of SPARC in prostate cancer metastasis to bone by reporting that SPARC recognition by prostate cancer cells promotes tumor growth and stimulates VEGF expression. The primary goal of this project is to extend our understanding of the role of SPARC in prostate cancer growth in bone. To address this, we will use a murine model of bone metastasis to investigate tumor growth in SPARC (-/-) mice. Tumor growth and bone remodeling will be visualized using a combination of MRI and micro CT imaging. Tumor tissue analysis will be used to detect phenotypic alterations of prostate cancer cells in the bone environment as a function of SPARC. Additionally, we will examine SPARC recognition by prostate cancer cells using recombinant SPARC and SPARC derived proteins. These studies will provide insight into the role of the bone matrix protein SPARC in prostate cancer growth in bone and may initiate studies on SPARC as a target of advanced prostate cancer therapy.
| McCabe, N Patrick; Kerr, Bethany A; Madajka, Maria et al. (2011) Augmented osteolysis in SPARC-deficient mice with bone-residing prostate cancer. Neoplasia 13:31-9 |
