Role of bone morphogenetic proteins in human prostate cancer pathogenesis and development of bone metastases: immunohistochemical study

Bone morphogenetic proteins (BMP) have the ability to induce ectopic bone formation. The findings of their expression in prostate cancers have been linked with specifically tumor progression to bone and development of osteosclerotic metastases. We investigated the expression pattern of BMP-2/4, -6 and -7 and the receptors BMPR-IA,-IB and -II in normal human prostate, organ-localized and metastatic prostate cancers. The expression we also examined in skeletal metastases caused by prostate cancer. In localized prostate cancers we found increased expression of BMP-6 and decreased expression of BMP-2/4 and -7. In metastatic prostate cancers the expression of examined BMPs decreased. The expression of BMPRs showed the tendency to be lower with progression of prostate cancer but the expression of BMPR-II was completely absent in metastatic prostate cancers. In bone metastases caused by prostate cancer we found high expression of BMP-2/4, -6 and -7. Decreased expression of BMPs and lose of BMPR-II expression, could suggest that the influence of BMPs on prostate cancer cells is inhibited and plays an important role in prostate cancer pathogenesis. High expression of osteogenic BMPs in prostate cancer bone metastases could explain their osteosclerotic properties.