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Br J Cancer. 2010 Jan 19;102(2):332-41. doi: 10.1038/sj.bjc.6605480. Epub 2009 Dec 15.

Prostate cancer cells modulate osteoblast mineralisation and osteoclast differentiation through Id-1.

Author information

1
Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong, China.

Abstract

BACKGROUND:

Id-1 is overexpressed in and correlated with metastatic potential of prostate cancer. The role of Id-1 in this metastatic process was further analysed.

METHODS:

Conditioned media from prostate cancer cells, expressing various levels of Id-1, were used to stimulate pre-osteoclast differentiation and osteoblast mineralisation. Downstream effectors of Id-1 were identified. Expressions of Id-1 and its downstream effectors in prostate cancers were studied using immunohistochemistry in a prostate cancer patient cohort (N=110).

RESULTS:

We found that conditioned media from LNCaP prostate cancer cells overexpressing Id-1 had a higher ability to drive osteoclast differentiation and a lower ability to stimulate osteoblast mineralisation than control, whereas conditioned media from PC3 prostate cancer cells with Id-1 knockdown were less able to stimulate osteoclast differentiation. Id-1 was found to negatively regulate TNF-beta and this correlation was confirmed in human prostate cancer specimens (P=0.03). Furthermore, addition of recombinant TNF-beta to LNCaP Id-1 cell-derived media blocked the effect of Id-1 overexpression on osteoblast mineralisation.

CONCLUSION:

In prostate cancer cells, the ability of Id-1 to modulate bone cell differentiation favouring metastatic bone disease is partially mediated by TNF-beta, and Id-1 could be a potential therapeutic target for prostate cancer to bone metastasis.

PMID:
20010941
PMCID:
PMC2816654
DOI:
10.1038/sj.bjc.6605480
[Indexed for MEDLINE]
Free PMC Article

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