The BMP antagonist Noggin is produced by osteoblasts in response to the presence of prostate cancer cells

Background Bone metastasis is a key event responsible for morbidity in prostate cancer patients. Interactions between prostate cancer cells and the bone microenvironment facilitate survival of tumour cells and alter bone turnover, a process that is thought to enhance the growth of metastases in this site. This study aimed to test the hypothesis that the presence of tumours cells increases TGFβ signaling in bone and that this regulates the proliferation and differentiation of osteoblastic lineage cells in metastatic sites. Results Initial studies showed that factors produced by prostate cancer cells increased the proliferation of osteoblastic cells and suppressed the early phase of their differentiation. We subsequently showed that interactions between prostate cancer and osteoblastic cells affected the expression of TGF-β superfamily genes in the latter. Noggin was expressed and secreted by prostate cancer cells but expressed at very low levels by osteoblastic cells when these cells were grown alone. This pattern changed when osteoblasic cells were treated with conditioned medium derived from prostate cancer cells or were co-cultured with the latter, with strong induction of Noggin being demonstrated. Immunohistochemical examination of prostate cancer xenografts showed strong Noggin protein staining on endosteal bone surfaces and in bone lining cells in close proximity to tumour foci. Conclusion These studies support previous work that suggest Noggin is an important suppressor of the differentiation of osteoblast lineage cells in bone metastases. Importantly we have now also shown that this protein can be induced in bone cells themselves by factors derived from prostate cancer cells. This article is protected by copyright. All rights reserved