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Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin

  • Authors:
    • Hisanori Uehara
    • Tetsuyuki Takahashi
    • Keisuke Izumi
  • View Affiliations / Copyright

    Affiliations: Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima-shi, Tokushima 770-8503, Japan
    Copyright: © Uehara et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 365-374
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    Published online on: May 24, 2013
       https://doi.org/10.3892/ijo.2013.1954
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Abstract

New drugs that inhibit the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL)/RANK pathway have demonstrated efficacy for the treatment of bone metastasis. Toxicities induced by these drugs, however, including osteonecrosis of the jaw and hypocalcemia, may adversely affect therapy. The aim of this study was to identify additional therapeutic targets that can be combined with OPG/RANKL/RANK pathway inhibition in the treatment of prostate cancer bone metastasis. We established a stable transfectant that produces high levels of OPG mRNA and protein from PC-3 human prostate cancer cells (PC3-OPG). The culture medium of PC3-OPG cells significantly inhibited the differentiation of mouse monocytes into mature osteoclasts. Furthermore, when PC3-OPG cells were injected into the bones of nude mice, bone destruction and tumor-induced osteoclast formation were reduced. Injection into bone of the mixtures containing equal amounts of green fluorescent protein (GFP)-expressing PC-3 cells (PC3-GFP) and PC3-OPG cells also reduced bone destruction, compared to the control mixture. PC3-GFP cells were subsequently isolated from bone tumors and used for microarray analysis to assess changes in gene expression following osteolytic tumor growth inhibition by OPG. We selected the top 10 upregulated genes based on results from microarrays and confirmed mRNA expression of each gene by RT-PCR. The expression patterns of retinol-binding protein 4 (RBP4) and placenta-specific 8 (PLAC8) were consistent with microarray results. Expression of these genes was also increased in the bone tumors of PC3-GFP/PC3-OPG-injected mice. Knockdown of both RBP4 and PLAC8 by siRNA inhibited the growth of PC-3 cells in vitro. Thus, RBP4 and PLAC8 may become new therapeutic targets for prostate cancer bone metastasis, in combination with OPG/RANKL/RANK pathway inhibition.
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Copy and paste a formatted citation
Spandidos Publications style
Uehara H, Takahashi T and Izumi K: Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin. Int J Oncol 43: 365-374, 2013.
APA
Uehara, H., Takahashi, T., & Izumi, K. (2013). Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin. International Journal of Oncology, 43, 365-374. https://doi.org/10.3892/ijo.2013.1954
MLA
Uehara, H., Takahashi, T., Izumi, K."Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin". International Journal of Oncology 43.2 (2013): 365-374.
Chicago
Uehara, H., Takahashi, T., Izumi, K."Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin". International Journal of Oncology 43, no. 2 (2013): 365-374. https://doi.org/10.3892/ijo.2013.1954
Copy and paste a formatted citation
x
Spandidos Publications style
Uehara H, Takahashi T and Izumi K: Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin. Int J Oncol 43: 365-374, 2013.
APA
Uehara, H., Takahashi, T., & Izumi, K. (2013). Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin. International Journal of Oncology, 43, 365-374. https://doi.org/10.3892/ijo.2013.1954
MLA
Uehara, H., Takahashi, T., Izumi, K."Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin". International Journal of Oncology 43.2 (2013): 365-374.
Chicago
Uehara, H., Takahashi, T., Izumi, K."Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin". International Journal of Oncology 43, no. 2 (2013): 365-374. https://doi.org/10.3892/ijo.2013.1954
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