Bone metastases are common complications of prostate cancer cells. The bone morphogenetic protein-2 (BMP-2) is constitutively secreted by osteoblasts and plays a key role in bone formation. Integrins are the major adhesive molecules in mammalian cells, and has been associated with cancer cells metastasis to bone. The aim of this study was to investigate whether osteoblast-derived BMP-2 is associated with prostate cancer metastasis.
Cancer cells migration activity was examined using the Transwell assay. The ERK and AKT phosphorylation was examined by using Western blot method. The siRNA was used to inhibit the expression of BMP-2. The cell surface expression of integrins was examined by using flow cytometry. A transient transfection protocol was used to examine NF-κB activity.
We found that osteoblast conditioned medium (OBCM) increased the migration and cell surface expression of β1 or β3 integrin in human prostate cancer cells. β1 or β3 integrin monoclonal antibodies or siRNA against β1 or β3 integrin inhibited the OBCM-induced increase the migration of prostate cancer cells. BMP-2 siRNA specifically reduced the OBCM-induced migration and integrins upregulation. BMP-2 siRNA also suppressed the OBCM-induced ERK, AKT and NF-κB activation.
This study suggest that the osteoblast-derived BMP-2 act through Akt and ERK, which in turn activates IKKα/β and NF-κB, resulting in the activations of β1 and β3 integrins and contributing the migration of prostate cancer cells. Prostate 68:1341–1353, 2008. © 2008 Wiley-Liss, Inc.