Metastatic Prostate Tumors in Bone
Prostate cancer frequently spreads or metastasizes to the skeleton. The growth of prostate cancer cells in bone causes bone destruction known as tumor-induced bone disease, which can lead to life-threatening conditions such as bone pain, nerve pain (spinal cord), stiffness, and even bone fractures. Our lab has previously shown that PC3 cells (metastatic prostate cancer) cultured on rigid 2D films express higher levels of genes that promote the metastatic and bone-destructive phenotype, particularly the transcription factor Gli2 and parathyroid hormone-related protein (PTHrP). We and others have also demonstrated that these metastatic cells overexpress integrin beta 3 (ITGB3) in the bone microenvironment. In order to study the expression of these genes in a more physiologically relevant environment, we created novel 3D scaffolds that mimic the trabecular structure of human bone at different sites including the femur, tibia, and vertebrae. In this study, we will culture PC3 cells on these scaffolds along with growth factors (TGF-β) and measure expression of Gli2, PTHrP, and ITGB3 via qRT-PCR and western blot. We will also measure gene expression after drug treatment with Gli2 inhibitors (GANT58) and ITGB3 inhibitors (cilengitide). We hypothesize that the trabecular structure of bone can modulate the expression of Gli2, PTHrP, and ITGB3 in prostate cancer cells to promote the metastatic and bone-destructive phenotype. A better understanding of tumor cell behavior in the bone microenvironment can help researchers develop new therapies to treat tumor-induced bone disease.