Abstract | BACKGROUND: The interaction between prostate cancer cells and osteoblasts is critical for the development of bone metastasis. Metastatic cancer cells may physically contact osteoblasts in the bone microenvironment; however, the biological significance of this interaction is not fully understood. METHODS: Human prostate cancer cells (the osteolytic cell line PC-3 and the osteoblastic cell line MDA-PCa 2b) and human osteoblasts (hFOB1.19) were cocultured under two different conditions (bilayer and contact conditions). Differential gene expression profiles of prostate cancer cells were then investigated using microarray analysis. Differentially expressed genes were analysed using RT-PCR and western blotting, and the effect of anti- cadherin neutralising antibodies on their expression was assayed. The osteoclastogenic activity of cells grown under these different conditions was also investigated using an in vitro assay. RESULTS: When PC-3 or MDA-PCa 2b cells were cocultured with hFOB1.19 cells under contact conditions, the expression of eight genes was upregulated and that of one gene was downregulated in PC-3 cells compared with gene expression in bilayer culture. No differentially expressed genes were detected in MDA-PCa 2b cells. Four of the eight upregulated genes ( interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), IL-6 and the third component of complement (C3)) have already been reported to participate in osteoclastogenesis. Indeed, a cell lysate of PC-3 cells grown under contact coculture conditions significantly enhanced osteoclastogenesis in vitro (P<0.005). neutralisation of cadherin-11 with a specific antibody inhibited upregulation of COX-2 and C3 mRNA in PC-3 cells. In contrast, neutralisation of N-cadherin induced upregulation of COX-2 mRNA. CONCLUSION:
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Authors | A Shiirevnyamba, T Takahashi, H Shan, H Ogawa, S Yano, H Kanayama, K Izumi, H Uehara |
Journal | British journal of cancer
(Br J Cancer)
Vol. 104
Issue 3
Pg. 505-13
(Feb 01 2011)
ISSN: 1532-1827 [Electronic] England |
PMID | 21206493
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- CDH2 protein, human
- Cadherins
- osteoblast cadherin
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Topics |
- Animals
- Antigens, CD
(metabolism)
- Bone Resorption
(metabolism)
- Cadherins
(metabolism)
- Cell Line, Tumor
- Gene Expression Profiling
- Humans
- Male
- Mice
- Mice, Nude
- Osteoblasts
(metabolism)
- Osteoclasts
(metabolism)
- Osteolysis
(metabolism)
- Prostatic Neoplasms
(metabolism)
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