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- Title
The BMP antagonist Noggin is produced by osteoblasts in response to the presence of prostate cancer cells.
- Authors
Alshaibi, Huda F.; Ahmed, Farid; Buckle, Clive; Fowles, Ann C. M.; Awlia, Jalaluddin; Cecchini, Marco G.; Eaton, Colby L.
- Abstract
Abstract: 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 tumor 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 tumors cells increases transforming growth factor beta (TGF‐β) signaling in bone and that this regulates the proliferation and differentiation of osteoblastic lineage cells in metastatic sites. 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 cocultured 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 tumor foci. 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.
- Subjects
BONE metastasis; NOGGIN (Protein); PROSTATE cancer patients; BONE morphogenetic proteins; OSTEOBLASTS
- Publication
Biotechnology & Applied Biochemistry, 2018, Vol 65, Issue 3, p407
- ISSN
0885-4513
- Publication type
Article
- DOI
10.1002/bab.1619