Secondini, Chiara; Wetterwald, Antoinette; Schwaninger, Ruth; Thalmann, George N.; Cecchini, Marco G (2011). The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis. PLoS ONE, 6(1), e16078. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0016078
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology |
UniBE Contributor: |
Thalmann, George, Cecchini, Marco Giovanni |
ISSN: |
1932-6203 |
Publisher: |
Public Library of Science |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:20 |
Last Modified: |
05 Dec 2022 14:05 |
Publisher DOI: |
10.1371/journal.pone.0016078 |
PubMed ID: |
21249149 |
Web of Science ID: |
000286515000016 |
BORIS DOI: |
10.7892/boris.6810 |
URI: |
https://boris.unibe.ch/id/eprint/6810 (FactScience: 211840) |
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