The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis

PLoS One. 2011 Jan 13;6(1):e16078. doi: 10.1371/journal.pone.0016078.


Members of the BMP and Wnt protein families play a relevant role in physiologic and pathologic bone turnover. Extracellular antagonists are crucial for the modulation of their activity. Lack of expression of the BMP antagonist noggin by osteoinductive, carcinoma-derived cell lines is a determinant of the osteoblast response induced by their bone metastases. In contrast, osteolytic, carcinoma-derived cell lines express noggin constitutively. We hypothesized that cancer cell-derived noggin may contribute to the pathogenesis of osteolytic bone metastasis of solid cancers by repressing bone formation. Intra-osseous xenografts of PC-3 prostate cancer cells induced osteolytic lesions characterized not only by enhanced osteoclast-mediated bone resorption, but also by decreased osteoblast-mediated bone formation. Therefore, in this model, uncoupling of the bone remodeling process contributes to osteolysis. Bone formation was preserved in the osteolytic lesions induced by noggin-silenced PC-3 cells, suggesting that cancer cell-derived noggin interferes with physiologic bone coupling. Furthermore, intra-osseous tumor growth of noggin-silenced PC-3 cells was limited, most probably as a result of the persisting osteoblast activity. This investigation provides new evidence for a model of osteolytic bone metastasis where constitutive secretion of noggin by cancer cells mediates inhibition of bone formation, thereby preventing repair of osteolytic lesions generated by an excess of osteoclast-mediated bone resorption. Therefore, noggin suppression may be a novel strategy for the treatment of osteolytic bone metastases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Proteins / antagonists & inhibitors*
  • Bone Neoplasms / etiology*
  • Bone Neoplasms / secondary
  • Bone Remodeling
  • Bone Resorption
  • Carrier Proteins / physiology*
  • Cell Line, Tumor
  • Humans
  • Male
  • Osteoblasts / pathology
  • Osteolysis / etiology*
  • Prostatic Neoplasms / pathology*
  • Signal Transduction*


  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • noggin protein