Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong, China.
Br J Cancer. 2010 Jan 19;102(2):332-41. doi: 10.1038/sj.bjc.6605480. Epub 2009 Dec 15.
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.
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).
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.
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.
Id-1 在前列腺癌的转移潜能中过度表达，并与之相关。进一步分析了 Id-1 在这个转移过程中的作用。
用表达不同水平 Id-1 的前列腺癌细胞的条件培养基来刺激前破骨细胞分化和成骨细胞矿化。鉴定 Id-1 的下游效应物。在前列腺癌患者队列（N=110）中，使用免疫组织化学研究前列腺癌中 Id-1 及其下游效应物的表达。
我们发现，过表达 Id-1 的 LNCaP 前列腺癌细胞的条件培养基具有更高的驱动破骨细胞分化的能力，而刺激成骨细胞矿化的能力较低，而 Id-1 敲低的 PC3 前列腺癌细胞的条件培养基则较难刺激破骨细胞分化。发现 Id-1 负调控 TNF-β，并且在人类前列腺癌标本中证实了这种相关性（P=0.03）。此外，将重组 TNF-β添加到 LNCaP Id-1 细胞衍生的培养基中可阻断 Id-1 过表达对成骨细胞矿化的影响。
在前列腺癌细胞中，Id-1 调节骨细胞分化以促进转移性骨疾病的能力部分由 TNF-β介导，Id-1 可能是前列腺癌向骨转移的潜在治疗靶点。
