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


CONCLUSIONS
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.
Yuen
H-F
HF
Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong, China.
Chiu
Y-T
YT
Chan
K-K
KK
Chan
Y-P
YP
Chua
C-W
CW
McCrudden
C M
CM
Tang
K-H
KH
El-Tanani
M
M
Wong
Y-C
YC
Wang
X
X
Chan
K-W
KW
D002113:Calcification, Physiologic / Q000502:physiology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis*; D008297:Male; D009362:Neoplasm Metastasis; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D011471:Prostatic Neoplasms
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1